chr12-109798820-G-T
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PM5PP2PP5_Moderate
The NM_021625.5(TRPV4):c.946C>A(p.Arg316Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R316H) has been classified as Pathogenic.
Frequency
Consequence
NM_021625.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
A variant that is likely pathogenic has been identified in the TRPV4 gene. The R316S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R316S variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R316S variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. Additionally, different missense variants at the same position (R316C and R316H) and a nearby residue (R315W) have been reported in Human Gene Mutation Database in association with TRPV-related disorders (Deng et al., 2010; Klein et al., 2011), supporting the functional importance of this region of the protein. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at