rs199756983
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5
The NM_032237.5(POMK):c.905T>A(p.Val302Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000805 in 1,614,058 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. V302V) has been classified as Likely benign.
Frequency
Consequence
NM_032237.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POMK | NM_032237.5 | c.905T>A | p.Val302Asp | missense_variant | 5/5 | ENST00000331373.10 | |
POMK | NM_001277971.2 | c.905T>A | p.Val302Asp | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POMK | ENST00000331373.10 | c.905T>A | p.Val302Asp | missense_variant | 5/5 | 2 | NM_032237.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152172Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251460Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135916
GnomAD4 exome AF: 0.0000869 AC: 127AN: 1461886Hom.: 0 Cov.: 33 AF XY: 0.0000770 AC XY: 56AN XY: 727242
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152172Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74336
ClinVar
Submissions by phenotype
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 2014 | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 10, 2019 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 03, 2017 | - - |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12;C4015184:Limb-girdle muscular dystrophy due to POMK deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 15, 2022 | 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. Experimental studies have shown that this missense change affects POMK function (PMID: 27879205). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 160349). This missense change has been observed in individual(s) with autosomal recessive Walker Warburg Syndrome (PMID: 24925318). This variant is present in population databases (rs199756983, gnomAD 0.009%). This sequence change replaces valine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 302 of the POMK protein (p.Val302Asp). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at