rs1200905474
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The ENST00000320356.7(EZH2):c.1178C>T(p.Thr393Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,613,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T393T) has been classified as Likely benign.
Frequency
Consequence
ENST00000320356.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EZH2 | NM_004456.5 | c.1178C>T | p.Thr393Met | missense_variant | 10/20 | ENST00000320356.7 | NP_004447.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EZH2 | ENST00000320356.7 | c.1178C>T | p.Thr393Met | missense_variant | 10/20 | 1 | NM_004456.5 | ENSP00000320147 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151914Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251370Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135848
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461864Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727240
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151914Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74164
ClinVar
Submissions by phenotype
Weaver syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 25, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 528797). This variant has not been reported in the literature in individuals affected with EZH2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 393 of the EZH2 protein (p.Thr393Met). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at