chr12-109814466-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_021625.5(TRPV4):c.331G>A(p.Gly111Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000682 in 1,614,000 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_021625.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152120Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251420Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135886
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461880Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9AN XY: 727242
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152120Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74314
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The p.G111S variant (also known as c.331G>A), located in coding exon 1 of the TRPV4 gene, results from a G to A substitution at nucleotide position 331. The glycine at codon 111 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Charcot-Marie-Tooth disease axonal type 2C Uncertain:1
Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TRPV4 protein function. 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. ClinVar contains an entry for this variant (Variation ID: 536861). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 111 of the TRPV4 protein (p.Gly111Ser). This variant is present in population databases (rs768721947, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with TRPV4-related conditions. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at