X-50088749-C-T
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001127898.4(CLCN5):c.1609C>T(p.Arg537Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,813 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001127898.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLCN5 | NM_001127898.4 | c.1609C>T | p.Arg537Ter | stop_gained | 12/15 | ENST00000376091.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLCN5 | ENST00000376091.8 | c.1609C>T | p.Arg537Ter | stop_gained | 12/15 | 2 | NM_001127898.4 | P3 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD4 exome AF: 9.11e-7 AC: 1AN: 1097813Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 363217
GnomAD4 genome Cov.: 23
ClinVar
Submissions by phenotype
not provided Pathogenic:4
Likely pathogenic, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Dec 30, 2022 | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 30586318, 25525159, 29084614, 15895257, 31597132, 16822791, 18184518, 31674016, 19076289, 20654030, 25907713, 19546586, 31328266, 32860533) - |
Pathogenic, no assertion criteria provided | research | Gharavi Laboratory, Columbia University | Sep 16, 2018 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Dent disease type 1 Pathogenic:1Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein | Aug 24, 2022 | ACMG classification criteria: PVS1 very strong, PS4 strong, PM2 moderated, PP1 supporting - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at