rs34954751
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001077365.2(POMT1):c.1692G>A(p.Arg564Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0283 in 1,612,506 control chromosomes in the GnomAD database, including 773 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.022 ( 55 hom., cov: 32)
Exomes 𝑓: 0.029 ( 718 hom. )
Consequence
POMT1
NM_001077365.2 synonymous
NM_001077365.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.111
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 Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
Variant 9-131520187-G-A is Benign according to our data. Variant chr9-131520187-G-A is described in ClinVar as [Benign]. Clinvar id is 130008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-131520187-G-A is described in Lovd as [Benign]. Variant chr9-131520187-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=0.111 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0217 (3302/152286) while in subpopulation NFE AF= 0.0309 (2105/68018). AF 95% confidence interval is 0.0298. There are 55 homozygotes in gnomad4. There are 1620 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 55 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
POMT1 | NM_001077365.2 | c.1692G>A | p.Arg564Arg | synonymous_variant | 17/20 | ENST00000402686.8 | NP_001070833.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0217 AC: 3302AN: 152168Hom.: 55 Cov.: 32
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GnomAD3 exomes AF: 0.0228 AC: 5711AN: 250686Hom.: 87 AF XY: 0.0232 AC XY: 3147AN XY: 135654
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GnomAD4 exome AF: 0.0290 AC: 42327AN: 1460220Hom.: 718 Cov.: 32 AF XY: 0.0285 AC XY: 20671AN XY: 726468
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GnomAD4 genome AF: 0.0217 AC: 3302AN: 152286Hom.: 55 Cov.: 32 AF XY: 0.0218 AC XY: 1620AN XY: 74450
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ClinVar
Significance: Benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:6
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 15, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 13, 2015 | p.Arg586Arg in exon 17 of POMT1: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 3.4% (291/8600) o f European American chromosomes by the NHLBI Exome Sequencing Project (http://ev s.gs.washington.edu/EVS/; dbSNP rs34954751). - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 21, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
not provided Benign:3
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Aug 28, 2017 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2K Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. - |
Walker-Warburg congenital muscular dystrophy;C1836373:Autosomal recessive limb-girdle muscular dystrophy type 2K;C5436962:Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at