rs7005111
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1
The NM_032237.5(POMK):c.618C>T(p.Asn206=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000237 in 1,614,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00015 ( 0 hom. )
Consequence
POMK
NM_032237.5 synonymous
NM_032237.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.70
Genes affected
POMK (HGNC:26267): (protein O-mannose kinase) This gene encodes a protein that may be involved in the presentation of the laminin-binding O-linked carbohydrate chain of alpha-dystroglycan (a-DG), which forms transmembrane linkages between the extracellular matrix and the exoskeleton. Some pathogens use this O-linked carbohydrate unit for host entry. Loss of function compound heterozygous mutations in this gene were found in a human patient affected by the Walker-Warburg syndrome (WWS) phenotype. Mice lacking this gene contain misplaced neurons (heterotopia) in some regions of the brain, possibly from defects in neuronal migration. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 8-43122442-C-T is Benign according to our data. Variant chr8-43122442-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 389687.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 = 0.00109 (166/152330) while in subpopulation AFR AF= 0.00363 (151/41570). AF 95% confidence interval is 0.00316. There are 0 homozygotes in gnomad4. There are 66 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POMK | NM_032237.5 | c.618C>T | p.Asn206= | synonymous_variant | 5/5 | ENST00000331373.10 | |
POMK | NM_001277971.2 | c.618C>T | p.Asn206= | synonymous_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POMK | ENST00000331373.10 | c.618C>T | p.Asn206= | synonymous_variant | 5/5 | 2 | NM_032237.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00108 AC: 164AN: 152212Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000331 AC: 83AN: 250628Hom.: 0 AF XY: 0.000244 AC XY: 33AN XY: 135466
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GnomAD4 exome AF: 0.000148 AC: 217AN: 1461830Hom.: 0 Cov.: 33 AF XY: 0.000124 AC XY: 90AN XY: 727214
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GnomAD4 genome ? AF: 0.00109 AC: 166AN: 152330Hom.: 0 Cov.: 33 AF XY: 0.000886 AC XY: 66AN XY: 74488
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 22, 2021 | - - |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12;C4015184:Limb-girdle muscular dystrophy due to POMK deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 04, 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