rs78529026
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001077365.2(POMT1):c.1585-14C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000685 in 1,610,622 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0031 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00044 ( 1 hom. )
Consequence
POMT1
NM_001077365.2 splice_polypyrimidine_tract, intron
NM_001077365.2 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.241
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
?
Variant 9-131520066-C-T is Benign according to our data. Variant chr9-131520066-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 167529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00305 (465/152316) while in subpopulation AFR AF= 0.0103 (429/41562). AF 95% confidence interval is 0.00952. There are 2 homozygotes in gnomad4. There are 212 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POMT1 | NM_001077365.2 | c.1585-14C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000402686.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POMT1 | ENST00000402686.8 | c.1585-14C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001077365.2 | P1 | |||
ENST00000415423.1 | n.62+2102G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00305 AC: 464AN: 152198Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000924 AC: 230AN: 248996Hom.: 0 AF XY: 0.000711 AC XY: 96AN XY: 134956
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GnomAD4 exome AF: 0.000437 AC: 638AN: 1458306Hom.: 1 Cov.: 31 AF XY: 0.000387 AC XY: 281AN XY: 725718
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 01, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 01, 2018 | 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, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 27, 2014 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2K Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
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 | Invitae | Jan 31, 2024 | - - |
Computational scores
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Name
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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