rs765230689
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001077365.2(POMT1):c.990T>A(p.Tyr330*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,613,952 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 Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001077365.2 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
POMT1 | NM_001077365.2 | c.990T>A | p.Tyr330* | stop_gained | 11/20 | ENST00000402686.8 | NP_001070833.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
POMT1 | ENST00000402686.8 | c.990T>A | p.Tyr330* | stop_gained | 11/20 | 1 | NM_001077365.2 | ENSP00000385797.4 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152124Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461828Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8AN XY: 727208
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152124Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74312
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2K;C4284790:Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1;C5436962:Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Walker-Warburg congenital muscular dystrophy;C1836373:Autosomal recessive limb-girdle muscular dystrophy type 2K;C5436962:Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 28, 2023 | This sequence change creates a premature translational stop signal (p.Tyr352*) in the POMT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in POMT1 are known to be pathogenic (PMID: 12369018, 15637732, 16575835). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Walker–Warburg syndrome (PMID: 15637732). ClinVar contains an entry for this variant (Variation ID: 502224). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 06, 2017 | - - |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Feb 05, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at