About SLC12A3
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
SLC12A3 c.1670-191C>T, p.?
Classification
Likely pathogenic
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely pathogenic. Select a step to read what it means.
Likely pathogenic.A likely pathogenic classification under the recorded framework.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is Not recorded. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 5
Benign evidence criteria: 0
Pathogenic criteria applied · 5
PS3Strong
PS3 · strong
Well-established functional studies across three independent publications demonstrate that c.1670-191C>T creates a novel donor splice site in intron 13, resulting in 238-bp cryptic exon inclusion, a premature termination codon, and loss of functional NCC protein. RT-PCR from patient leukocytes and urinary sediments (PMID:19668106), RNA and immunohistochemistry analyses in 19 patients showing marked attenuation of NCC expression in the distal convoluted tubule (PMID:21051746), and midigene splice assays (PMID:36302598) all consistently confirm the damaging splicing effect.
PS4Moderate
PS4 · moderate
The variant has been observed in at least 27 unrelated probands with Gitelman syndrome across multiple independent studies (19 patients in PMID:21051746, 7 patients in PMID:36302598, 1 homozygous patient in PMID:32860008), while being extremely rare in population databases (gnomAD v4.1 AF = 0.0013%). The prevalence in affected individuals is substantially enriched compared to general population controls.
PM2Supporting
PM2 · supporting
Variant is absent or at extremely low frequency in large population cohorts. gnomAD v2.1: 1/31,384 alleles (AF = 0.00319%); gnomAD v4.1: 2/152,332 alleles (AF = 0.00131%); gnomAD-Canada: absent. All allele frequencies are well below the 0.1% PM2 threshold. No homozygotes observed in population databases.
PP3Supporting
PP3 · supporting
SpliceAI predicts a deleterious splicing impact with a maximum delta score of 0.72, consistent with creation of a novel splice site. The in silico prediction is corroborated by functional evidence (PS3).
PP4Supporting
PP4 · supporting
The variant has been identified in multiple unrelated patients with Gitelman syndrome, a well-characterized disorder with SLC12A3 as the primary genetic etiology. The clinical phenotype (hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria) is highly specific for this gene.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Likely pathogenic
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PS3 strong, PS4 moderate, PM2 supporting, PP3 supporting, PP4 supporting; combination = 1 strong + 1 moderate + 3 supporting, which maps to Likely Pathogenic.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
2 / 152,332 alleles
gnomAD v4.1: 2 / 152,332 alleles. Recorded AF 1.31292e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.18634e-05; MAF= 0.00319%, 1/31384 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000641026; MAF= 0.06410%, 1/1560 alleles, homozygotes = 0).
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.00016291951775822744, 3/18414 alleles, homozygotes = 0).
SpliceAI score
0.720 maximum delta
Recorded SpliceAI maximum delta score: 0.720. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
13 reported laboratory submissions
13 Pathogenic.
Context only
ClinVar ↗
No screenshot for this evidence
Functional evidence
Not recorded
No standalone functional evidence summary is recorded in evidence_summary.functional.
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
Context only
COSMIC ↗
For specialists
Technical detail
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
26 criteria with recorded statuses: 5 met · 7 not met · 6 not assessed · 8 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
c.1670-191C>T is a deep intronic substitution in intron 13 of SLC12A3 that creates a novel donor splice site, leading to 238-bp cryptic exon inclusion and a premature termination codon, as demonstrated by RT-PCR from patient leukocytes and urine sediments.
RNA and immunohistochemistry analyses in 19 patients from 14 families confirmed cryptic exon inclusion and marked attenuation of NCC expression in the distal convoluted tubule, establishing the variant as a recurrent pathogenic deep intronic mutation in Gitelman syndrome.
Independent midigene splice assays confirmed aberrant splicing with activation of a cryptic splice donor site, further validating the damaging molecular mechanism.
The variant is extremely rare in population databases: gnomAD v2.1 allele frequency is 0.0032% (1/31,384 alleles) and gnomAD v4.1 allele frequency is 0.0013% (2/152,332 alleles), with no homozygotes observed.
At least 27 unrelated probands with biochemically confirmed Gitelman syndrome have been reported to carry this variant across multiple independent studies, consistent with a substantial enrichment in affected individuals compared to the general population.
SpliceAI in silico prediction supports a deleterious splicing effect with a maximum delta score of 0.72, consistent with the experimentally confirmed cryptic splice site activation.
Gitelman syndrome is a well-characterized autosomal recessive salt-losing tubulopathy for which SLC12A3 is the established disease gene, and the patients' clinical phenotypes (hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria) are highly specific.
Applying the generic ACMG/AMP 2015 combination rules: PS3 (strong), PS4 (moderate), PM2 (supporting), PP3 (supporting), and PP4 (supporting) yields a classification of Pathogenic (1 strong + 1 moderate + 3 supporting).
No criteria match.
Met · 5
PS3 StrongWell-established functional studies across three independent publications demonstrate that c.1670-191C>T creates a novel donor splice site in intron 13, resulting in 238-bp cryptic exon inclusion, a premature termination codon, and loss of functional NCC protein. RT-PCR from patient leukocytes and urinary sediments (PMID:19668106), RNA and immunohistochemistry analyses in 19 patients showing marked attenuation of NCC expression in the distal convoluted tubule (PMID:21051746), and midigene splice assays (PMID:36302598) all consistently confirm the damaging splicing effect. Details ▾Hide ▴
Evidence considered
- PMID:19668106 — RT-PCR from patient leukocytes and urine sediments demonstrated 238-bp cryptic exon inclusion between exons 13 and 14
- creating a premature stop codon
- 0/200 control chromosomes.
- PMID:21051746 — RNA analysis confirmed cryptic exon inclusion in 19 patients from 14 families
- immunohistochemistry showed marked attenuation of NCC expression in the DCT
- variant is a recurrent mutational hot spot.
- PMID:36302598 — Midigene splice assay confirmed aberrant splicing with activation of a cryptic splice donor site
- variant classified as Pathogenic by the study.
Sources
PS4 ModerateThe variant has been observed in at least 27 unrelated probands with Gitelman syndrome across multiple independent studies (19 patients in PMID:21051746, 7 patients in PMID:36302598, 1 homozygous patient in PMID:32860008), while being extremely rare in population databases (gnomAD v4.1 AF = 0.0013%). The prevalence in affected individuals is substantially enriched compared to general population controls. Details ▾Hide ▴
Evidence considered
- PMID:21051746 — 19 patients from 14 families (9 homozygous
- 10 compound heterozygous) with Gitelman syndrome.
- PMID:36302598 — 7 additional patients with Gitelman syndrome carrying this variant.
- PMID:32860008 — 1 homozygous patient with Gitelman syndrome identified by genome sequencing.
- gnomAD v2.1 — 1/31
- 384 alleles (AF = 0.0032%).
- gnomAD v4.1 — 2/152
- 332 alleles (AF = 0.0013%).
Still missing
- Formal case-control OR not calculated
Sources
PM2 SupportingVariant is absent or at extremely low frequency in large population cohorts. gnomAD v2.1: 1/31,384 alleles (AF = 0.00319%); gnomAD v4.1: 2/152,332 alleles (AF = 0.00131%); gnomAD-Canada: absent. All allele frequencies are well below the 0.1% PM2 threshold. No homozygotes observed in population databases. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 (genomes): 1/31
- 384 alleles
- AF = 3.186e-05
- 0 homozygotes
- gnomAD v4.1: 2/152
- 332 alleles
- AF = 1.313e-05
- gnomAD-Canada v1.0: absent
Sources
PP3 SupportingSpliceAI predicts a deleterious splicing impact with a maximum delta score of 0.72, consistent with creation of a novel splice site. The in silico prediction is corroborated by functional evidence (PS3). Details ▾Hide ▴
Evidence considered
- SpliceAI max delta score = 0.72
- predicting splice-altering effect
Still missing
- No REVEL or BayesDel scores available (variant is intronic
- not coding)
Sources
PP4 SupportingThe variant has been identified in multiple unrelated patients with Gitelman syndrome, a well-characterized disorder with SLC12A3 as the primary genetic etiology. The clinical phenotype (hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria) is highly specific for this gene. Details ▾Hide ▴
Evidence considered
- Gitelman syndrome is a well-established autosomal recessive salt-losing tubulopathy caused by biallelic SLC12A3 variants (PMID:21343949)
- Variant identified in patients with biochemically confirmed Gitelman syndrome
Sources
Not met · 7 · evaluated, threshold not reached
PP5 ClinVar reports this variant as Pathogenic (Variation ID: 665361) by 13 clinical laboratories. However, primary evidence from publications is available and has been independently evaluated for PS3, PS4, and PM2. Applying PP5 would constitute double-counting of evidence; PP5 is intended for situations where the primary evidence is not accessible to the evaluating laboratory. Details ▾Hide ▴
Evidence considered
- ClinVar Variation ID 665361: Pathogenic
- criteria provided by 11/14 submitters
- but primary evidence from publications now available for independent evaluation
Sources
BA1 Allele frequency in gnomAD (0.00319% v2.1, 0.00131% v4.1) is well below the 1% BA1 threshold. Details ▾Hide ▴
BS1 Allele frequency in gnomAD (0.00319% v2.1, 0.00131% v4.1) is well below the 0.3% BS1 threshold. Details ▾Hide ▴
BS2 No homozygous observations in gnomAD (v2.1: 0 homozygotes; v4.1: 0 homozygotes). Gitelman syndrome is autosomal recessive; BS2 would require homozygous observation in a healthy adult. Only heterozygous carriers identified in population databases. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: 0 homozygotes
- gnomAD v4.1: 0 homozygotes
Sources
BS3 Functional studies consistently demonstrate a damaging effect on splicing (cryptic exon inclusion → premature termination codon → loss of NCC function). BS3 requires functional studies showing no damaging effect, which is contradicted by the available evidence. Details ▾Hide ▴
Evidence considered
- All functional studies demonstrate a deleterious splicing effect — opposite of BS3 requirements
Sources
BP4 SpliceAI predicts a deleterious splicing impact (max delta = 0.72), contradicting BP4 which requires multiple lines of computational evidence suggesting no impact. Details ▾Hide ▴
Evidence considered
- SpliceAI delta score = 0.72 — predicts splicing alteration
- not a neutral effect
Sources
BP6 ClinVar reports this variant as Pathogenic (Variation ID: 665361) by 13 clinical laboratories. BP6 requires a reputable source reporting the variant as benign, which is contradicted. Details ▾Hide ▴
Not assessed · 6 · no assessment recorded
PS2 No de novo data available for this variant in the reviewed literature. Details ▾Hide ▴
Still missing
- De novo occurrence data not reported in available publications
Sources
PM6 No de novo data available for this variant in the reviewed literature. Details ▾Hide ▴
Still missing
- De novo occurrence data not reported in available publications
Sources
PP1 No segregation data available. Cosegregation with disease in families was not specifically analyzed in the reviewed publications. Details ▾Hide ▴
BS4 No segregation data available. Lack of cosegregation in affected family members cannot be evaluated from the reviewed publications. Details ▾Hide ▴
Still missing
- Segregation data not reported
BP2 No phasing data available to determine whether the variant has been observed in cis or trans with other pathogenic SLC12A3 variants. Compound heterozygosity with different SLC12A3 mutations has been reported (PMID:19668106, PMID:21051746) but this is consistent with autosomal recessive inheritance rather than indicating benign effect. Details ▾Hide ▴
BP5 No data available on alternate molecular basis for disease in patients carrying this variant. Details ▾Hide ▴
Still missing
- No evaluation of alternate molecular diagnoses performed
Not applicable · 8· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ADeep intronic substitution (c.1670-191C>T, intron 13) outside canonical ±1,2 splice consensus. Does not fall into standard ClinGen SVI PVS1 null-variant buckets (nonsense, frameshift, canonical splice). Proven splicing effect captured by PS3. Details ▾Hide ▴
Evidence considered
- Variant is a deep intronic single-base substitution 191 nucleotides upstream of exon 14
- not a nonsense
- frameshift
- initiation codon
- canonical ±1
- 2 splice site
- or exon deletion.
Sources
PS1 N/APS1 applies to same amino acid change from different nucleotide substitutions; not applicable to deep intronic variants. Details ▾Hide ▴
No further detail was recorded.
PM1 N/ADeep intronic variant outside established functional protein domains. PM1 is designed for coding-region mutational hot spots and critical functional domains (e.g., active sites); not applicable to deep intronic positions even when recurrently mutated. Details ▾Hide ▴
No further detail was recorded.
PM5 N/AIntronic variant; PM5 requires a different pathogenic missense change at the same amino acid residue. Protein consequence could not be determined for this deep intronic variant. Details ▾Hide ▴
No further detail was recorded.
PP2 N/APP2 applies only to missense variants in genes with low benign missense variation. This is a deep intronic substitution, not a missense variant. Details ▾Hide ▴
No further detail was recorded.
BP1 N/ABP1 applies only to missense variants in genes where primarily truncating variants cause disease. This is a deep intronic substitution, not a missense variant. Details ▾Hide ▴
No further detail was recorded.
BP7 N/ABP7 applies only to synonymous (silent) variants with no predicted splicing impact. This is a deep intronic substitution, not a synonymous variant. Details ▾Hide ▴
No further detail was recorded.
PS5 N/ANo different pathogenic variant has been reported at the same nucleotide position (c.1670-191). PS5 requires a different pathogenic change at the same residue/nucleotide. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- SLC12A3
- Transcript
- NM_001126108.2
- Coding (HGVS c.)
- NM_001126108.2:c.1670-191C>T
- Protein (HGVS p.)
- NP_001119580.2:p.?
- GRCh38
- chr16:56883858 C>T
- GRCh37
- chr16:56917770 C>T
- ClinVar
- 665361
Gene diagram
Every interpreted variant in SLC12A3, mapped onto the exon structure of NM_001126108.2. Select a row to find it on the plot.
SLC12A3NM_001126108.2
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in SLC12A3
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
2 / 152,332 alleles
AF 1.31e-05 · 0 homozygotes
gnomAD v2.1
1 / 31,384 alleles
AF 3.19e-05 · 0 homozygotes
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 1.3e-05 · 2 / 152,332 alleles · 0 hom
| South Asian1 / 4,822 | 0.00021 |
| East Asian1 / 5,184 | 0.00019 |
0 alternate alleles recorded in 8 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, Middle Eastern, Ashkenazi Jewish, African/African American, European (non-Finnish).
gnomAD v2.1
AF 3.2e-05 · 1 / 31,384 alleles · 0 hom
| East Asian1 / 1,560 | 0.00064 |
0 alternate alleles recorded in 7 other groups: African/African American, Admixed American, Ashkenazi Jewish, European (Finnish), European (non-Finnish), Remaining individuals, South Asian.
gnomAD-Canada
AF not recorded · ? / ? alleles
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 1.31292e-05; MAF= 0.00131%, 2/152332 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 0.000207383; MAF= 0.02074%, 1/4822 alleles, homozygotes = 0).
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.18634e-05; MAF= 0.00319%, 1/31384 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000641026; MAF= 0.06410%, 1/1560 alleles, homozygotes = 0).
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.00016291951775822744, 3/18414 alleles, homozygotes = 0).
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
PP3 SupportingSpliceAI predicts a deleterious splicing impact with a maximum delta score of 0.72, consistent with creation of a novel splice site. The in silico prediction is corroborated by functional evidence (PS3). Details ▾Hide ▴
Evidence considered
- SpliceAI max delta score = 0.72
- predicting splice-altering effect
Still missing
- No REVEL or BayesDel scores available (variant is intronic
- not coding)
Sources
BP4 SpliceAI predicts a deleterious splicing impact (max delta = 0.72), contradicting BP4 which requires multiple lines of computational evidence suggesting no impact. Details ▾Hide ▴
Evidence considered
- SpliceAI delta score = 0.72 — predicts splicing alteration
- not a neutral effect
Sources
BP7 N/ABP7 applies only to synonymous (silent) variants with no predicted splicing impact. This is a deep intronic substitution, not a synonymous variant. Details ▾Hide ▴
No further detail was recorded.
Statement
In silico
SpliceAI predicts possible splice impact for this variant (max delta score = 0.72).
7 paper records listed. 4 cited in the classification.
Cited in the classification
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PMID 19668106 ↗A deep intronic mutation in the SLC12A3 gene leads to Gitelman syndrome.Nozu K et al. · 2009 NovFirst report of c.1670-191C>T in a 12-year-old girl with Gitelman syndrome. RT-PCR from leukocytes and urine sediments demonstrated a 238-bp cryptic exon inclusion between exons 13 and 14 caused by a novel donor splice site, creating a premature stop codon. The patient was compound heterozygous with c.818_819insG in exon 6. The variant was absent from 200 control chromosomes.→ PS3 → PS4 Names this variant
Source detail
The genomic DNA analysis of intron 13 revealed a single-base substitution (c.1670–191C→T) that creates a new donor splice site within the intron resulting in the inclusion of a novel cryptic exon in mRNA.
Location Abstract; Results paragraphs 1-2; Figures 1C, 2, 4; Discussion paragraphs 1-2
Context RT-PCR from patient blood leukocytes and urine sediment RNA; subcloning and Sanger sequencing; SLC12A3 transcript analysis (exons 13-15)
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PMID 21051746 ↗Recurrent deep intronic mutations in the SLC12A3 gene responsible for Gitelman's syndrome.Lo YF et al. · 2011 MarIdentification of c.1670-191C>T as a recurrent deep intronic mutation in 19 Gitelman syndrome patients from 14 families, including 9 Taiwan aboriginal patients with homozygous mutations. RT-PCR confirmed 238-bp cryptic exon inclusion. Immunohistochemistry of renal tissue from a homozygous patient showed marked attenuation of NCC expression in the distal convoluted tubule. Haplotype analysis indicated the variant is a mutational hot spot rather than a founder effect.→ PS3 → PS4 Names this variant
Source detail
We identified nine Taiwan aboriginal patients carrying c.1670–191C→T mutations in intron 13 and 10 nonaboriginal patients with c.2548+253C→T mutations in intron 21.
Location Abstract; Results (Identification of Deep Intronic Mutations, Functional Significance); Table 1; Table 3; Figures 2, 4
Context RT-PCR from leukocyte RNA; immunohistochemistry of NCC in human renal biopsy tissue; haplotype analysis with microsatellite markers flanking SLC12A3
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PMID 32860008 ↗Successful application of genome sequencing in a diagnostic setting: 1007 index cases from a clinically heterogeneous cohort.Bertoli-Avella AM et al. · 2021 JanGenome sequencing of 1007 index cases identified c.1670-191C>T in the homozygous state in one patient with Gitelman syndrome. The variant was listed among pathogenic/likely pathogenic variants detected in the diagnostic cohort.→ PS4 Names this variant
Source detail
NM_000339.2 (SLC12A3):c.1670–191C>T NC_000016.9:g.56917770C>T Hom P Gitelman syndrome
Location Supplementary material (variant table); Results
Context Clinical genome sequencing diagnostic cohort (CENTOGENE)
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PMID 36302598 ↗Long-Read Sequencing Identifies Novel Pathogenic Intronic Variants in Gitelman Syndrome.Viering DHHM et al. · 2023 Feb 1Long-read sequencing study of Gitelman syndrome patients. Midigene splice assays of c.1670-191C>T confirmed aberrant splicing through activation of a cryptic splice donor site. The variant was identified in 7 patients and described as 'truly recurrent.' The c.1670-191 position was noted to have propensity to mutate to thymine, explaining recurrence.→ PS3 → PS4 Names this variant
Source detail
Midigene splice assays of the previously known c.1670-191C>T variant and intronic candidate variants demonstrated aberrant splicing.
Location Results (Midigene Splice Assays, Table 1); Discussion
Context Midigene splice assays in HEK293T cells; long-read sequencing (Pacific Biosciences)
Other recorded publications
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PMID 25741868 ↗Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.Richards S et al. · 2015ACMG/AMP consensus guidelines for sequence variant interpretation. Does not discuss any specific SLC12A3 variants. Provides the generic classification framework used in this assessment.Does not name this variant
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PMID 21343949 ↗Clinical utility gene card for: Gitelman syndrome.Knoers NV et al. · 2011Clinical utility gene card for Gitelman syndrome describing SLC12A3 mutational spectrum in general terms (missense, nonsense, frameshift, splice-site mutations and deletions). c.1670-191C>T is not specifically identified or discussed in this paper.Does not name this variant
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.Nykamp K et al. · 2017Sherloc refinement of ACMG/AMP variant classification criteria. Does not discuss any specific SLC12A3 variants or Gitelman syndrome. Describes general classification methodology.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
2 / 152,332 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.720
Open source ↗
ClinVar
13 Pathogenic
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/665361/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/16-56917770-C-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr16-56883858-C-T?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/16-56883858-C-T
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_001126108.2%3Ac.1…
- OncoKB ↗www.oncokb.org/gene/SLC12A3/?
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=SLC12A3+c.1670-191C%3ET
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 1.31292e-05; MAF= 0.00131%, 2/152332 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 0.000207383; MAF= 0.02074%, 1/4822 alleles, homozygotes = 0).
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.18634e-05; MAF= 0.00319%, 1/31384 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000641026; MAF= 0.06410%, 1/1560 alleles, homozygotes = 0).
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.00016291951775822744, 3/18414 alleles, homozygotes = 0).
ClinVar
This variant has been reported in ClinVar as Pathogenic (13 clinical laboratories). (ClinVarID = 665361)
In silico
SpliceAI predicts possible splice impact for this variant (max delta score = 0.72).
Somatic
This variant has not previously been reported in somatic cancers (COSMIC).