X-53533365-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PM5PP2PP3_Moderate
The NM_031407.7(HUWE1):c.13069C>T(p.Arg4357Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000166 in 1,206,317 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R4357H) has been classified as Likely pathogenic.
Frequency
Consequence
NM_031407.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HUWE1 | NM_031407.7 | c.13069C>T | p.Arg4357Cys | missense_variant | 84/84 | ENST00000262854.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HUWE1 | ENST00000262854.11 | c.13069C>T | p.Arg4357Cys | missense_variant | 84/84 | 1 | NM_031407.7 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00000900 AC: 1AN: 111116Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33316
GnomAD4 exome AF: 9.13e-7 AC: 1AN: 1095201Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0AN XY: 360631
GnomAD4 genome AF: 0.00000900 AC: 1AN: 111116Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33316
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 01, 2021 | Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at