9-114424459-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_015404.4(WHRN):c.1291C>T(p.Arg431Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,702 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R431Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_015404.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WHRN | NM_015404.4 | c.1291C>T | p.Arg431Trp | missense_variant | 6/12 | ENST00000362057.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WHRN | ENST00000362057.4 | c.1291C>T | p.Arg431Trp | missense_variant | 6/12 | 1 | NM_015404.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250962Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135710
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461524Hom.: 0 Cov.: 37 AF XY: 0.00000688 AC XY: 5AN XY: 727076
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74354
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 29, 2012 | The Arg431Trp variant (DFNB31) has not been reported in the literature nor previ ously identified by our laboratory. Computational analyses (biochemical amino ac id properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the Ar g431Trp variant may impact the protein, though this information is not predictiv e enough to determine pathogenicity. In summary, the clinical significance of th is variant cannot be determined with certainty. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at