About EZHIP
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
EZHIP c.1272G>A, p.(Gln424=)
Classification
Likely benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely benign. Select a step to read what it means.
Likely benign.A likely benign 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: 0
Benign evidence criteria: 3
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 3
BS1Supporting
BS1 · supporting
gnomAD v2.1 grpmax filtering allele frequency is 0.47% (East Asian AF 0.54%) with 1 homozygote, exceeding the 0.3% threshold expected for a rare disease variant. gnomAD v4.1 grpmax FAF of 0.19% falls below the threshold, introducing some uncertainty; strength reduced to supporting benign to reflect this discrepancy and the uncertain disease prevalence for EZHIP.
BP4Supporting
BP4 · supporting
Multiple lines of computational evidence suggest no impact. SpliceAI predicts no splicing effect (max delta=0.02, well below 0.1 threshold). The variant is synonymous (p.Gln424=) with no predicted protein change. REVEL and BayesDel are unavailable but the consistent benign in silico profile supports BP4.
BP7Supporting
BP7 · supporting
Synonymous variant (NP_981952.1:p.(Gln424=)) with SpliceAI max delta score of 0.02, predicting no impact on splicing or creation of a novel splice site. Nucleotide-level conservation data are not available, but the absent splice prediction supports a silent effect.
Recorded classification: Likely benign
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: BS1 supporting benign, BP4 supporting benign, BP7 supporting benign; combination = 3 supporting benign, which maps to Likely Benign.
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
81 / 569,401 alleles
gnomAD v4.1: 81 / 569,401 alleles. Recorded AF 0.000142255. Recorded homozygote count 1.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000400055; MAF= 0.04001%, 82/204972 alleles, homozygotes = 1) and has highest observed frequency in the East Asian population (AF= 0.00539265; MAF= 0.53927%, 80/14835 alleles, homozygotes = 1); grpmax FAF= 0.00468821.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.000414651002073255, 6/14470 alleles, homozygotes = 0).
SpliceAI score
0.020 maximum delta
Recorded SpliceAI maximum delta score: 0.020. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
Not recorded
A ClinVar laboratory submission summary was not recorded.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
27 criteria with recorded statuses: 3 met · 19 not met · 0 not assessed · 5 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_203407.3:c.1272G>A (p.Gln424=) is a synonymous variant in EZHIP exon 1. SpliceAI predicts no splicing impact (max delta=0.02), consistent with a silent substitution.
This variant is present in gnomAD v2.1 with a grpmax filtering allele frequency of 0.47% (82/204,972 alleles, 1 homozygote) and an East Asian subpopulation frequency of 0.54% (80/14,835 alleles, 1 homozygote), exceeding the 0.3% threshold expected for a rare disease variant and supporting a benign interpretation.
The variant is absent from ClinVar and has not been reported in the published literature. No functional studies, segregation data, or case-control evidence exists to support pathogenicity.
No pathogenic criteria are met. Benign evidence includes BS1 (supporting benign; population frequency), BP4 (supporting benign; in silico predictions), and BP7 (supporting benign; synonymous with silent splice prediction). Overall, the variant is classified as Likely Benign.
No criteria match.
Met · 3
BS1 SupportinggnomAD v2.1 grpmax filtering allele frequency is 0.47% (East Asian AF 0.54%) with 1 homozygote, exceeding the 0.3% threshold expected for a rare disease variant. gnomAD v4.1 grpmax FAF of 0.19% falls below the threshold, introducing some uncertainty; strength reduced to supporting benign to reflect this discrepancy and the uncertain disease prevalence for EZHIP. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: grpmax FAF=0.47%
- East Asian AF=0.54%
- 82/204972 alleles
- 1 homozygote
- gnomAD v4.1: grpmax FAF=0.19%
- East Asian AF=0.23%
- 81/569401 alleles
- gnomAD-Canada: absent
Still missing
- v4.1 grpmax FAF (0.19%) is below 0.3% threshold
- discordant with v2.1. EZHIP disease prevalence is not well established.
Sources
BP4 SupportingMultiple lines of computational evidence suggest no impact. SpliceAI predicts no splicing effect (max delta=0.02, well below 0.1 threshold). The variant is synonymous (p.Gln424=) with no predicted protein change. REVEL and BayesDel are unavailable but the consistent benign in silico profile supports BP4. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta=0.02 (no splice impact predicted)
- Synonymous variant with no amino acid change
- REVEL/BayesDel unavailable
Still missing
- REVEL and BayesDel scores unavailable for this position.
Sources
BP7 SupportingSynonymous variant (NP_981952.1:p.(Gln424=)) with SpliceAI max delta score of 0.02, predicting no impact on splicing or creation of a novel splice site. Nucleotide-level conservation data are not available, but the absent splice prediction supports a silent effect. Details ▾Hide ▴
Evidence considered
- Synonymous variant p.(Gln424=)
- no amino acid change
- SpliceAI max delta=0.02 (no splice impact predicted)
Still missing
- Nucleotide conservation data not available.
Sources
Not met · 19 · evaluated, threshold not reached
PS1 No pathogenic variant has been reported at this nucleotide position (NM_203407.3:c.1272) in ClinVar or the published literature. No same-site comparator exists. Details ▾Hide ▴
Evidence considered
- Variant is absent from ClinVar
- no pathogenic classification at this position.
Sources
PS2 No de novo observation has been reported for this variant in any publication or database. Details ▾Hide ▴
Evidence considered
- No de novo evidence identified
- variant absent from ClinVar and literature.
Sources
PS3 No well-established in vitro or in vivo functional studies have been identified for this variant. OncoKB reports Unknown Oncogenic Effect with no supporting PMIDs. Details ▾Hide ▴
Evidence considered
- OncoKB: Unknown Oncogenic Effect
- no supporting literature. No functional studies identified.
Still missing
- No functional studies exist for this variant.
Sources
PS4 No case-control or case series data exist for this variant. The variant is absent from ClinVar and no publications mention it. Details ▾Hide ▴
Evidence considered
- Variant absent from ClinVar. No published case reports or case-control studies identified.
Sources
PM1 This variant does not lie in a statistically significant mutational hotspot or a well-established critical functional domain without benign variation. Details ▾Hide ▴
Evidence considered
- Hotspot analysis: variant not in a statistically significant hotspot.
PM2 Although total gnomAD v2.1 allele frequency is 0.04% (below 0.1% threshold), the grpmax filtering allele frequency is 0.47% with 1 homozygote, exceeding the 0.1% rarity threshold. This variant is not sufficiently rare to meet PM2. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: total AF=0.04%
- grpmax FAF=0.47%
- East Asian AF=0.54%
- 1 homozygote
- gnomAD v4.1: total AF=0.014%
- grpmax FAF=0.19%
- East Asian AF=0.23%
Sources
PM6 No confirmed de novo observation (with maternity and paternity confirmed) has been reported for this variant. Details ▾Hide ▴
PP1 No segregation data are available for this variant in affected families. Details ▾Hide ▴
Evidence considered
- No segregation studies identified.
Still missing
- No family-based segregation data.
PP3 Multiple lines of computational evidence do not support a deleterious effect. SpliceAI predicts no splicing impact (max delta=0.02). REVEL and BayesDel scores are unavailable for this variant. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta=0.02 (no significant splice impact)
- REVEL: not available
- BayesDel: not available
Still missing
- REVEL and BayesDel scores unavailable for chrX at this position.
Sources
PP4 No patient phenotype or clinical data are available for this variant. No case reports exist in the literature. Details ▾Hide ▴
Evidence considered
- No clinical phenotype data available. Variant absent from ClinVar.
Sources
PP5 No reputable source has classified this variant as pathogenic. The variant is absent from ClinVar. Details ▾Hide ▴
Evidence considered
- Absent from ClinVar. No expert panel or clinical laboratory has reported this variant as pathogenic.
Sources
BA1 No population allele frequency exceeds 1%. Highest subpopulation frequency is East Asian at 0.54% in gnomAD v2.1 (below 1% BA1 threshold). Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 max subpopulation AF: 0.54% (East Asian)
- gnomAD v4.1 max subpopulation AF: 0.23% (East Asian)
Sources
BS2 No direct evidence that this variant has been observed in healthy adults for a disorder with full penetrance. EZHIP disease association and penetrance are not well established. Details ▾Hide ▴
Evidence considered
- No individual-level phenotype data from gnomAD carriers. Uncertain penetrance for EZHIP-associated disease.
Still missing
- EZHIP disease penetrance not established.
BS3 No well-established in vitro or in vivo functional studies demonstrate no damaging effect for this synonymous variant. Details ▾Hide ▴
Evidence considered
- No functional studies identified. OncoKB: Unknown Oncogenic Effect.
Still missing
- No functional characterization of this variant.
Sources
BS4 No segregation data are available to demonstrate lack of cosegregation with disease in affected families. Details ▾Hide ▴
Evidence considered
- No family-based segregation studies identified.
BP2 No evidence of this variant observed in trans with a pathogenic variant for a dominant disorder, or in cis with a pathogenic variant for a recessive disorder. Details ▾Hide ▴
Evidence considered
- No phase data available.
BP5 No evidence that this variant has been observed in a case where an alternate molecular basis for disease was identified. Details ▾Hide ▴
Evidence considered
- No case data with alternate molecular diagnoses.
BP6 No reputable source has classified this variant as benign. The variant is absent from ClinVar. Details ▾Hide ▴
Evidence considered
- Absent from ClinVar. No expert panel or clinical laboratory has classified this variant.
Sources
PS5 No evidence this variant has been observed in trans with a known pathogenic variant in a recessive disorder. Details ▾Hide ▴
Not applicable · 5· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ASynonymous variant (NP_981952.1:p.(Gln424=)) does not fall into any PVS1 null-variant category (nonsense, frameshift, or canonical ±1,2 splice consensus). ClinGen SVI PVS1 decision tree does not apply. Details ▾Hide ▴
Evidence considered
- Variant is synonymous
- predicted protein is unchanged.
Sources
pvs1_variant_assessmentpvs1_gene_context
PM5 N/ASynonymous variant (p.Gln424=) produces no amino acid change. PM5 requires a different pathogenic missense change at the same residue and does not apply to synonymous variants. Details ▾Hide ▴
Evidence considered
- Protein consequence is p.(Gln424=)
- no residue change. PM5 not applicable.
Sources
pm5_candidates
PP2 N/APP2 applies to missense variants in genes with a low rate of benign missense variation where missense variants are a common disease mechanism. This variant is synonymous, not missense. Details ▾Hide ▴
Evidence considered
- Variant is synonymous (p.Gln424=)
- not missense.
BP1 N/ABP1 applies to missense variants in genes where primarily truncating variants cause disease. This variant is synonymous, not missense. Details ▾Hide ▴
Evidence considered
- Variant is synonymous (p.Gln424=)
- not missense.
BP3 N/AVariant is a substitution, not an in-frame indel. BP3 applies only to in-frame deletions or insertions in non-repeat regions. Details ▾Hide ▴
Evidence considered
- Substitution variant
- not applicable.
Identifiers
- Gene
- EZHIP
- Transcript
- NM_203407.3
- Coding (HGVS c.)
- NM_203407.3:c.1272G>A
- Protein (HGVS p.)
- NP_981952.1:p.(Gln424=)
- GRCh38
- chrX:51408288 G>A
- GRCh37
- chrX:51151140 G>A
Gene diagram
Every interpreted variant in EZHIP, mapped onto the exon structure of NM_203407.3. Select a row to find it on the plot.
EZHIPNM_203407.3
Fetching transcript structure from UCSC…
Exons
—
Transcript span
—
Strand
—
Variants mapped
—
Source
UCSC ncbiRefSeqCurated
All variants in EZHIP
—
Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
81 / 569,401 alleles
AF 0.000142 · 1 homozygotes · FAF 0.00191
gnomAD v2.1
82 / 204,972 alleles
AF 0.0004 · 1 homozygotes · FAF 0.00469
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 0.00014 · 81 / 569,401 alleles · 1 hom · FAF 0.0019
| East Asian72 / 30,704 | 0.00231 hom |
| Remaining individuals7 / 26,445 | 0.00026 |
| South Asian1 / 44,788 | 2.2e-05 |
| Admixed American1 / 45,068 | 2.2e-05 |
0 alternate alleles recorded in 6 other groups: European (Finnish), Amish, Middle Eastern, Ashkenazi Jewish, African/African American, European (non-Finnish).
gnomAD v2.1
AF 0.0004 · 82 / 204,972 alleles · 1 hom · FAF 0.0047
| East Asian80 / 14,835 | 0.00541 hom |
| Remaining individuals1 / 5,334 | 0.00019 |
| South Asian1 / 19,053 | 5.2e-05 |
0 alternate alleles recorded in 5 other groups: African/African American, Admixed American, Ashkenazi Jewish, European (Finnish), European (non-Finnish).
gnomAD-Canada
AF not recorded · ? / ? alleles
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.000142255; MAF= 0.01423%, 81/569401 alleles, homozygotes = 1) and has highest observed frequency in the East Asian population (AF= 0.00234497; MAF= 0.23450%, 72/30704 alleles, homozygotes = 1); grpmax FAF= 0.00190909.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000400055; MAF= 0.04001%, 82/204972 alleles, homozygotes = 1) and has highest observed frequency in the East Asian population (AF= 0.00539265; MAF= 0.53927%, 80/14835 alleles, homozygotes = 1); grpmax FAF= 0.00468821.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.000414651002073255, 6/14470 alleles, homozygotes = 0).
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
BP4 SupportingMultiple lines of computational evidence suggest no impact. SpliceAI predicts no splicing effect (max delta=0.02, well below 0.1 threshold). The variant is synonymous (p.Gln424=) with no predicted protein change. REVEL and BayesDel are unavailable but the consistent benign in silico profile supports BP4. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta=0.02 (no splice impact predicted)
- Synonymous variant with no amino acid change
- REVEL/BayesDel unavailable
Still missing
- REVEL and BayesDel scores unavailable for this position.
Sources
BP7 SupportingSynonymous variant (NP_981952.1:p.(Gln424=)) with SpliceAI max delta score of 0.02, predicting no impact on splicing or creation of a novel splice site. Nucleotide-level conservation data are not available, but the absent splice prediction supports a silent effect. Details ▾Hide ▴
Evidence considered
- Synonymous variant p.(Gln424=)
- no amino acid change
- SpliceAI max delta=0.02 (no splice impact predicted)
Still missing
- Nucleotide conservation data not available.
Sources
PP3 Multiple lines of computational evidence do not support a deleterious effect. SpliceAI predicts no splicing impact (max delta=0.02). REVEL and BayesDel scores are unavailable for this variant. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta=0.02 (no significant splice impact)
- REVEL: not available
- BayesDel: not available
Still missing
- REVEL and BayesDel scores unavailable for chrX at this position.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02).
0 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
81 / 569,401 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.020
Open source ↗
ClinVar
Captured ClinVar source record
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/?term=NM_203407.3%3Ac.1272G%3EA
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/X-51151140-G-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chrX-51408288-G-A?dataset=gnomad_r4
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/X-51408288-G-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_203407.3%3Ac.1272…
- OncoKB ↗www.oncokb.org/gene/EZHIP/Q424=
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=EZHIP+c.1272G%3EA
- Cancer hotspots ↗www.cancerhotspots.org/
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= 0.000142255; MAF= 0.01423%, 81/569401 alleles, homozygotes = 1) and has highest observed frequency in the East Asian population (AF= 0.00234497; MAF= 0.23450%, 72/30704 alleles, homozygotes = 1); grpmax FAF= 0.00190909.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000400055; MAF= 0.04001%, 82/204972 alleles, homozygotes = 1) and has highest observed frequency in the East Asian population (AF= 0.00539265; MAF= 0.53927%, 80/14835 alleles, homozygotes = 1); grpmax FAF= 0.00468821.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.000414651002073255, 6/14470 alleles, homozygotes = 0).
ClinVar
This variant is absent from ClinVar.
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02).
Functional
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.