9-131523037-ACT-ACTCT
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP5_Moderate
The NM_001077365.2(POMT1):c.2113_2114dupTC(p.Pro706fs) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Consequence
POMT1
NM_001077365.2 frameshift
NM_001077365.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.82
Genes affected
POMT1 (HGNC:9202): (protein O-mannosyltransferase 1) The protein encoded by this gene is an O-mannosyltransferase that requires interaction with the product of the POMT2 gene for enzymatic function. The encoded protein is found in the membrane of the endoplasmic reticulum. Defects in this gene are a cause of Walker-Warburg syndrome (WWS) and limb-girdle muscular dystrophy type 2K (LGMD2K). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0289 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 9-131523037-A-ACT is Pathogenic according to our data. Variant chr9-131523037-A-ACT is described in ClinVar as [Pathogenic]. Clinvar id is 280761.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
POMT1 | NM_001077365.2 | c.2113_2114dupTC | p.Pro706fs | frameshift_variant | 20/20 | ENST00000402686.8 | NP_001070833.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 34
GnomAD4 exome
Cov.:
34
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Aug 10, 2016 | The c.2179_2180dupTC pathogenic variant in the POMT1 gene causes a frameshift starting with codon Proline 728, changes this amino acid to an Arginine residue and creates a premature Stop codon at position 17 of the new reading frame, denoted p.Pro728ArgfsX17. This pathogenic variant is predicted to cause loss of normal protein function through protein truncation, as the last 20 amino acids are replaced with 16 incorrect amino acids. Furthermore, c.2179_2180dupTC was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Although this variant has not been reported previously to our knowledge, other frameshift variants have been reported in the Human Gene Mutation Database in association with POMT1-related disorders (Stenson et al., 2014). Therefore, c.2179_2180dupTC is considered a pathogenic variant. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at