rs541606391
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 8P and 9B. PVS1BP6BS1BS2
The NM_021625.5(TRPV4):c.1656del(p.Tyr553ThrfsTer8) variant causes a frameshift, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000465 in 1,613,662 control chromosomes in the GnomAD database, including 3 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_021625.5 frameshift, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRPV4 | NM_021625.5 | c.1656del | p.Tyr553ThrfsTer8 | frameshift_variant, splice_region_variant | 10/16 | ENST00000261740.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRPV4 | ENST00000261740.7 | c.1656del | p.Tyr553ThrfsTer8 | frameshift_variant, splice_region_variant | 10/16 | 1 | NM_021625.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000506 AC: 77AN: 152096Hom.: 1 Cov.: 31
GnomAD3 exomes AF: 0.000577 AC: 145AN: 251256Hom.: 0 AF XY: 0.000501 AC XY: 68AN XY: 135846
GnomAD4 exome AF: 0.000461 AC: 673AN: 1461448Hom.: 2 Cov.: 31 AF XY: 0.000413 AC XY: 300AN XY: 727052
GnomAD4 genome ? AF: 0.000506 AC: 77AN: 152214Hom.: 1 Cov.: 31 AF XY: 0.000645 AC XY: 48AN XY: 74434
ClinVar
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | TRPV4: BS1, BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 24, 2021 | This variant is associated with the following publications: (PMID: 25473036) - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Aug 26, 2016 | - - |
Charcot-Marie-Tooth disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, London Health Sciences Centre | - | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 18, 2019 | 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
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 20, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at