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EZHIPc.741A>TLikely benign
Print report
Variant interpretation report

EZHIP c.741A>T, p.(Pro247=)

NM_203407.3:c.741A>T NP_981952.1:p.(Pro247=) View identifiers
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.

About EZHIP

No gene-level summary was recorded for this case.

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: 1 Benign evidence criteria: 2
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting

NM_203407.3:c.741A>T is absent from gnomAD v2.1, v4.1, and gnomAD-Canada v1.0, consistent with a rare variant. However, as a synonymous variant with no predicted splice or functional impact, the absence from population databases provides limited evidence of pathogenicity; applied at supporting strength.

Benign criteria applied · 2
BP4Supporting
BP4 · supporting

Multiple lines of computational evidence suggest NM_203407.3:c.741A>T has no impact on the gene product. SpliceAI predicts no significant splice impact (max delta score = 0.02, well below the standard 0.2 threshold). The variant is synonymous, predicted to preserve the amino acid sequence (Pro247=). No in silico tool predicts a deleterious effect.

BP7Supporting
BP7 · supporting

NM_203407.3:c.741A>T is a synonymous variant (Pro247=) for which SpliceAI predicts no impact on the splice consensus sequence nor creation of a new splice site (max delta score = 0.02, acceptor gain DS_AG = 0.02, all other deltas = 0.0). Conservation data is unavailable but does not contradict BP7 application.

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: PM2 supporting, BP4 supporting benign, BP7 supporting benign; combination = 1 supporting + 2 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.

SpliceAI score
0.020 maximum delta

Recorded SpliceAI maximum delta score: 0.020. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · BP4, BP7 → SpliceAI ↗
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
COSMIC ↗Cancer Hotspots ↗
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 · 15 not met · 0 not assessed · 9 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic
PVS1PS1PS2PS3PS4PM1PM2PM5PM6PP1PP2PP3PP4PP5PS5
Benign
BA1BS1BS2BS3BS4BP1BP2BP3BP4BP5BP6BP7
Met Not met Not assessed Not applicable

NM_203407.3:c.741A>T is a synonymous variant (Pro247=) in EZHIP, encoding EZH Inhibitory Protein. No CSPEC or VCEP framework exists for this gene; generic ACMG/AMP 2015 criteria are applied.

This variant is absent from all population databases including gnomAD v2.1, v4.1, and gnomAD-Canada (PM2 at supporting strength, discounted for synonymous variant with no predicted functional impact).

Multiple lines of computational evidence suggest no impact on the gene product: SpliceAI predicts no splice alteration (max delta 0.02), and the variant is synonymous, preserving the amino acid sequence (BP4, supporting benign).

The variant satisfies BP7 criteria as a synonymous variant with no predicted splice impact per SpliceAI (supporting benign).

Overall, one supporting pathogenic criterion (PM2) and two supporting benign criteria (BP4, BP7) are met. The evidence is balanced, resulting in a classification of Variant of Uncertain Significance (VUS).

Met · 3

PM2 SupportingNM_203407.3:c.741A>T is absent from gnomAD v2.1, v4.1, and gnomAD-Canada v1.0, consistent with a rare variant. However, as a synonymous variant with no predicted splice or functional impact, the absence from population databases provides limited evidence of pathogenicity; applied at supporting strength. Details ▾Hide ▴
Evidence considered
  • Absent from gnomAD v2.1 (AF=0).
  • Absent from gnomAD v4.1 (AF=0).
  • Absent from gnomAD-Canada v1.0 (AF=0).
Still missing
  • Synonymous variant with no functional impact prediction
  • population absence is less informative.
Sources
gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗
BP4 SupportingMultiple lines of computational evidence suggest NM_203407.3:c.741A>T has no impact on the gene product. SpliceAI predicts no significant splice impact (max delta score = 0.02, well below the standard 0.2 threshold). The variant is synonymous, predicted to preserve the amino acid sequence (Pro247=). No in silico tool predicts a deleterious effect. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta = 0.02 (no predicted splice alteration).
  • Synonymous variant (Pro247=) predicted to preserve protein sequence.
  • No REVEL or BayesDel score to suggest deleteriousness.
Still missing
  • REVEL and BayesDel scores unavailable
  • lacking additional orthogonal in silico evidence.
Sources
spliceai ↗
BP7 SupportingNM_203407.3:c.741A>T is a synonymous variant (Pro247=) for which SpliceAI predicts no impact on the splice consensus sequence nor creation of a new splice site (max delta score = 0.02, acceptor gain DS_AG = 0.02, all other deltas = 0.0). Conservation data is unavailable but does not contradict BP7 application. Details ▾Hide ▴
Evidence considered
  • Synonymous variant with no amino acid change (Pro247=).
  • SpliceAI max delta = 0.02
  • no predicted splice site creation or disruption.
  • SpliceAI delta scores: DS_AG=0.02
  • DS_AL=0.0
  • DS_DG=0.0
  • DS_DL=0.0.
Still missing
  • Nucleotide conservation (PhyloP/GERP) data unavailable.
Sources
spliceai ↗

Not met · 15 · evaluated, threshold not reached

PS2 No de novo observations have been reported for NM_203407.3:c.741A>T in any available data source. Details ▾Hide ▴
Evidence considered
  • No de novo evidence identified in literature or databases.
Still missing
  • No parental testing data available.
PS3 No functional studies have been identified for NM_203407.3:c.741A>T. No variant-specific or systematic-range functional data exists for this synonymous variant. Details ▾Hide ▴
Evidence considered
  • No functional data available for this variant.
Still missing
  • No functional assays performed for this variant.
PS4 No case-control or statistical evidence supports enrichment of this variant in affected individuals. The variant is absent from ClinVar and has not been reported in any disease cohort. Details ▾Hide ▴
Evidence considered
  • Absent from ClinVar
  • no case-control data available.
Still missing
  • No cohort studies or case-control data identified.
Sources
clinvar ↗
PM1 NM_203407.3:c.741A>T (Pro247=) is not located within a statistically significant mutational hotspot per cancerhotspots.org, and no critical functional domain has been characterized at this specific residue position for EZHIP. Details ▾Hide ▴
Evidence considered
  • cancerhotspots.org: residue not significant
  • no domain-level evidence for pathogenicity at codon 247.
Still missing
  • Limited functional domain annotation for EZHIP at this residue.
PM6 No de novo observation has been reported for NM_203407.3:c.741A>T. Details ▾Hide ▴
Evidence considered
  • No de novo data identified.
Still missing
  • No parental testing data available.
PP1 No segregation data is available for NM_203407.3:c.741A>T. Details ▾Hide ▴
Evidence considered
  • No family segregation studies identified.
Still missing
  • No family data available for cosegregation analysis.
PP3 Multiple in silico tools do not predict a deleterious effect. SpliceAI predicts no significant splice impact (max delta score = 0.02, well below the 0.2 threshold). REVEL and BayesDel scores are not available for this variant. Available computational evidence does not support a pathogenic role. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta = 0.02 (no predicted splice impact).
  • Synonymous variant not predicted to alter amino acid sequence.
  • REVEL and BayesDel scores not available.
Still missing
  • REVEL and BayesDel scores unavailable
  • limited conservation data.
Sources
spliceai ↗
PP4 No phenotype specificity data is available for NM_203407.3:c.741A>T. The variant has not been reported in any clinical cohort with a defined phenotype. Details ▾Hide ▴
Evidence considered
  • No phenotype data available.
Still missing
  • No clinical phenotype information associated with this variant.
BA1 NM_203407.3:c.741A>T is absent from gnomAD v2.1 and v4.1 (allele frequency = 0). The BA1 threshold of >1% in population databases is not met. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1: AF = 0.
  • gnomAD v4.1: AF = 0.
Sources
gnomad_v2 ↗gnomad_v4 ↗
BS1 NM_203407.3:c.741A>T is absent from gnomAD (AF = 0). The BS1 threshold of >0.3% allele frequency in population databases is not met. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1: AF = 0.
  • gnomAD v4.1: AF = 0.
Sources
gnomad_v2 ↗gnomad_v4 ↗
BS2 No homozygous adult observations or unaffected carrier data have been reported for NM_203407.3:c.741A>T. Details ▾Hide ▴
Evidence considered
  • No homozygous or unaffected carrier data available.
Still missing
  • No data on homozygous or unaffected carrier observations.
BS3 No functional studies have been performed demonstrating that NM_203407.3:c.741A>T has no deleterious effect. No well-established in vitro or in vivo assays exist for this variant. Details ▾Hide ▴
Evidence considered
  • No functional data available demonstrating no deleterious effect.
Still missing
  • No functional studies for this variant.
BS4 No segregation data is available to evaluate lack of cosegregation with disease for NM_203407.3:c.741A>T. Details ▾Hide ▴
Evidence considered
  • No family segregation data available.
Still missing
  • No family studies to assess segregation.
BP2 No observation of NM_203407.3:c.741A>T in trans with a pathogenic variant has been reported. Details ▾Hide ▴
Evidence considered
  • No in trans observation data available.
Still missing
  • No phase information available.
BP5 No case has been identified in which NM_203407.3:c.741A>T is found alongside an alternate molecular basis for disease. Details ▾Hide ▴
Evidence considered
  • No alternate molecular diagnosis data available.
Still missing
  • No data on cases with alternate molecular basis.
Not applicable · 9· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_203407.3:c.741A>T is a synonymous variant (NP_981952.1:p.(Pro247=)) with no predicted null effect on protein function. It does not fall into any PVS1 null-variant bucket (nonsense, frameshift, or canonical ±1,2 splice consensus variants) per ClinGen SVI PVS1 recommendations (PMC6185798). Details ▾Hide ▴
Evidence considered
  • Synonymous variant (Pro247=) with no predicted truncation or splice disruption.
Sources
pvs1_generic_framework ↗
PS1 N/AThis is a synonymous variant with no amino acid change. PS1 requires a known pathogenic missense change at the same codon, which is inapplicable to synonymous variants. Details ▾Hide ▴
Evidence considered
  • Synonymous variant (Pro247=)
  • no pathogenic amino acid change at this position.
PM5 N/ANo missense comparator variant exists at the same residue. NM_203407.3:c.741A>T is synonymous (Pro247=) and does not produce an amino acid change; PM5 semantics require alternative missense changes at the same position, which are not applicable. Details ▾Hide ▴
Evidence considered
  • Synonymous variant
  • no amino acid substitution to compare.
PP2 N/APP2 applies specifically to missense variants in genes with a low rate of benign missense variation. NM_203407.3:c.741A>T is a synonymous variant and does not qualify. Details ▾Hide ▴
Evidence considered
  • Synonymous variant
  • PP2 is missense-specific.
PP5 N/ANM_203407.3:c.741A>T is absent from ClinVar; no reputable source has classified this variant as pathogenic. No 3-star expert panel classification exists. Details ▾Hide ▴
Evidence considered
  • Absent from ClinVar
  • no classifications available.
Sources
clinvar ↗
BP1 N/ABP1 applies specifically to missense variants in genes where primarily truncating variants cause disease. NM_203407.3:c.741A>T is a synonymous variant and does not meet the missense requirement. Details ▾Hide ▴
Evidence considered
  • Synonymous variant
  • BP1 is missense-specific.
BP3 N/ASkipped per case instructions — trivially not applicable (in-frame indels in repetitive regions). Details ▾Hide ▴

No further detail was recorded.

BP6 N/ANM_203407.3:c.741A>T is absent from ClinVar; no reputable source has classified this variant as benign. No 3-star expert panel classification exists. Details ▾Hide ▴
Evidence considered
  • Absent from ClinVar
  • no benign classifications available.
Sources
clinvar ↗
PS5 N/AThis variant is absent from ClinVar; no classification by an expert panel or multiple submitters exists to satisfy PS5. Details ▾Hide ▴
Evidence considered
  • Absent from ClinVar with no classifications.
Sources
clinvar ↗

Identifiers

Gene
EZHIP
Transcript
NM_203407.3
Coding (HGVS c.)
NM_203407.3:c.741A>T
Protein (HGVS p.)
NP_981952.1:p.(Pro247=)
GRCh38
chrX:51407757 A>T
GRCh37
chrX:51150609 A>T

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…
gnomAD v4.1 Allele count data not recorded
gnomAD v2.1 Allele count data not recorded
gnomAD-Canada v1.0 Allele count data not recorded

Statements

gnomAD v4.1

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

SpliceAI and Pangolin

SpliceAI acceptor lossat +36 bp
0.000
SpliceAI acceptor gainat +20 bp
0.020
SpliceAI donor lossat +245 bp
0.000
SpliceAI donor gainat -117 bp
0.000
Pangolin splice lossmagnitude shown
-0.000
Pangolin splice gain
0.010

Other predictors

REVEL
Not available
BayesDel
Not available

How the predictions were used

BP4 SupportingMultiple lines of computational evidence suggest NM_203407.3:c.741A>T has no impact on the gene product. SpliceAI predicts no significant splice impact (max delta score = 0.02, well below the standard 0.2 threshold). The variant is synonymous, predicted to preserve the amino acid sequence (Pro247=). No in silico tool predicts a deleterious effect. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta = 0.02 (no predicted splice alteration).
  • Synonymous variant (Pro247=) predicted to preserve protein sequence.
  • No REVEL or BayesDel score to suggest deleteriousness.
Still missing
  • REVEL and BayesDel scores unavailable
  • lacking additional orthogonal in silico evidence.
Sources
spliceai ↗
BP7 SupportingNM_203407.3:c.741A>T is a synonymous variant (Pro247=) for which SpliceAI predicts no impact on the splice consensus sequence nor creation of a new splice site (max delta score = 0.02, acceptor gain DS_AG = 0.02, all other deltas = 0.0). Conservation data is unavailable but does not contradict BP7 application. Details ▾Hide ▴
Evidence considered
  • Synonymous variant with no amino acid change (Pro247=).
  • SpliceAI max delta = 0.02
  • no predicted splice site creation or disruption.
  • SpliceAI delta scores: DS_AG=0.02
  • DS_AL=0.0
  • DS_DG=0.0
  • DS_DL=0.0.
Still missing
  • Nucleotide conservation (PhyloP/GERP) data unavailable.
Sources
spliceai ↗
PP3 Multiple in silico tools do not predict a deleterious effect. SpliceAI predicts no significant splice impact (max delta score = 0.02, well below the 0.2 threshold). REVEL and BayesDel scores are not available for this variant. Available computational evidence does not support a pathogenic role. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta = 0.02 (no predicted splice impact).
  • Synonymous variant not predicted to alter amino acid sequence.
  • REVEL and BayesDel scores not available.
Still missing
  • REVEL and BayesDel scores unavailable
  • limited conservation data.
Sources
spliceai ↗

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 Captured gnomAD v4.1 source record 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

Statements for reports

The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.

gnomAD v4.1

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

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.