rs119462984
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001077365.2(POMT1):āc.1680G>Cā(p.Trp560Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W560R) has been classified as Uncertain significance.
Frequency
Consequence
NM_001077365.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POMT1 | NM_001077365.2 | c.1680G>C | p.Trp560Cys | missense_variant | 17/20 | ENST00000402686.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POMT1 | ENST00000402686.8 | c.1680G>C | p.Trp560Cys | missense_variant | 17/20 | 1 | NM_001077365.2 | P1 | |
ENST00000415423.1 | n.62+1993C>G | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461314Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 726966
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 2006 | - - |
Walker-Warburg congenital muscular dystrophy;C1836373:Autosomal recessive limb-girdle muscular dystrophy type 2K;C5436962:Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 01, 2022 | This missense change has been observed in individual(s) with POMT1-related conditions (PMID: 16575835). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 582 of the POMT1 protein (p.Trp582Cys). ClinVar contains an entry for this variant (Variation ID: 3242). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at