rs727505127
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_015404.4(WHRN):c.725G>A(p.Arg242His) variant causes a missense change. The variant allele was found at a frequency of 0.00000682 in 1,613,062 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R242C) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WHRN | NM_015404.4 | c.725G>A | p.Arg242His | missense_variant | 2/12 | ENST00000362057.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WHRN | ENST00000362057.4 | c.725G>A | p.Arg242His | missense_variant | 2/12 | 1 | NM_015404.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152210Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000804 AC: 2AN: 248802Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134684
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1460852Hom.: 0 Cov.: 31 AF XY: 0.00000826 AC XY: 6AN XY: 726686
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74350
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 | Jun 21, 2014 | The Arg242His variant in DFNB31has not been previously reported in individuals w ith hearing loss and was absent from large population studies. Computational pre diction tools and conservation analysis suggest that the Arg242His variant may n ot impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the Arg242His varia nt is uncertain. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 25, 2022 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 242 of the WHRN protein (p.Arg242His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with WHRN-related conditions. ClinVar contains an entry for this variant (Variation ID: 179786). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at