12-109788632-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP6BS1BS2
The NM_021625.5(TRPV4):c.1976C>T(p.Ser659Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000632 in 1,614,126 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. S659S) has been classified as Likely benign.
Frequency
Consequence
NM_021625.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRPV4 | NM_021625.5 | c.1976C>T | p.Ser659Leu | missense_variant | 13/16 | ENST00000261740.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRPV4 | ENST00000261740.7 | c.1976C>T | p.Ser659Leu | missense_variant | 13/16 | 1 | NM_021625.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000138 AC: 21AN: 152240Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251418Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135890
GnomAD4 exome AF: 0.0000554 AC: 81AN: 1461886Hom.: 0 Cov.: 33 AF XY: 0.0000564 AC XY: 41AN XY: 727240
GnomAD4 genome ? AF: 0.000138 AC: 21AN: 152240Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12AN XY: 74370
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 19, 2021 | 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 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Sep 10, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 02, 2019 | - - |
Charcot-Marie-Tooth disease Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, London Health Sciences Centre | - | - - |
Spondylometaphyseal dysplasia, Kozlowski type;C0265281:Metatropic dysplasia;C0432227:Brachyrachia (short spine dysplasia);C0751335:Scapuloperoneal spinal muscular atrophy;C1838492:Neuronopathy, distal hereditary motor, autosomal dominant 8;C1847406:Familial digital arthropathy-brachydactyly;C1853710:Charcot-Marie-Tooth disease axonal type 2C;C1868616:Parastremmatic dwarfism;C3150755:Sodium serum level quantitative trait locus 1;C3159322:Spondyloepimetaphyseal dysplasia, Maroteaux type;C4479260:Avascular necrosis of femoral head, primary, 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 07, 2020 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Charcot-Marie-Tooth disease axonal type 2C Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 05, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at