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rs567303957

chr8-43122433-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_032237.5(POMK):c.609C>T(p.Cys203=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000219 in 1,614,132 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00020 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

POMK
NM_032237.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.27
Variant links:
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 Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-43122433-C-T is Benign according to our data. Variant chr8-43122433-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 541243.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.27 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
POMKNM_032237.5 linkuse as main transcriptc.609C>T p.Cys203= synonymous_variant 5/5 ENST00000331373.10
POMKNM_001277971.2 linkuse as main transcriptc.609C>T p.Cys203= synonymous_variant 4/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
POMKENST00000331373.10 linkuse as main transcriptc.609C>T p.Cys203= synonymous_variant 5/52 NM_032237.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000204
AC:
31
AN:
152198
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000458
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.000578
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000250
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000307
AC:
77
AN:
250556
Hom.:
0
AF XY:
0.000325
AC XY:
44
AN XY:
135428
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000260
Gnomad ASJ exome
AF:
0.0000995
Gnomad EAS exome
AF:
0.000870
Gnomad SAS exome
AF:
0.000392
Gnomad FIN exome
AF:
0.000139
Gnomad NFE exome
AF:
0.000292
Gnomad OTH exome
AF:
0.000491
GnomAD4 exome
AF:
0.000220
AC:
322
AN:
1461816
Hom.:
0
Cov.:
33
AF XY:
0.000221
AC XY:
161
AN XY:
727214
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000224
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.000403
Gnomad4 SAS exome
AF:
0.000325
Gnomad4 FIN exome
AF:
0.0000562
Gnomad4 NFE exome
AF:
0.000221
Gnomad4 OTH exome
AF:
0.000182
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000204
AC:
31
AN:
152316
Hom.:
1
Cov.:
33
AF XY:
0.000215
AC XY:
16
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000458
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.000580
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000250
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000183
Hom.:
0
Bravo
AF:
0.000204
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000273
EpiControl
AF:
0.000533

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12;C4015184:Limb-girdle muscular dystrophy due to POMK deficiency Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJan 18, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.61
Cadd
Benign
0.28
Dann
Benign
0.77
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs567303957; hg19: chr8-42977576; COSMIC: COSV58856442; COSMIC: COSV58856442; API