rs56282240

chr8-43122706-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_032237.5(POMK):c.882G>A(p.Gly294=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000891 in 1,614,136 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00093 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00089 (1 hom.)
• Consequence: POMK NM_032237.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.138

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 8-43122706-G-A is Benign according to our data. Variant chr8-43122706-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 474197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.138 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMK	NM_032237.5	c.882G>A	p.Gly294=	synonymous_variant	5/5	ENST00000331373.10
POMK	NM_001277971.2	c.882G>A	p.Gly294=	synonymous_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMK	ENST00000331373.10	c.882G>A	p.Gly294=	synonymous_variant	5/5	2	NM_032237.5	P1

Frequencies

GnomAD3 genomes AF: 0.000933 AC: 142 AN: 152154 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00107

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00105 AC: 264 AN: 251444 Hom.: 0 AF XY: 0.000949 AC XY: 129 AN XY: 135896

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00377

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00194

Gnomad NFE exome AF: 0.00142

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000887 AC: 1296 AN: 1461864 Hom.: 1 Cov.: 33 AF XY: 0.000862 AC XY: 627 AN XY: 727230

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.000246

Gnomad4 ASJ exome AF: 0.00287

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000185

Gnomad4 FIN exome AF: 0.00168

Gnomad4 NFE exome AF: 0.000930

Gnomad4 OTH exome AF: 0.00113

GnomAD4 genome AF: 0.000933 AC: 142 AN: 152272 Hom.: 1 Cov.: 33 AF XY: 0.00116 AC XY: 86 AN XY: 74448

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00283

Gnomad4 NFE AF: 0.00107

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00128 Hom.: 0

Bravo AF: 0.000680

EpiCase AF: 0.000927

EpiControl AF: 0.000711

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	POMK: BP4, BP7 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2021	- -

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 submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	6.2
Dann	Benign	0.74

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

Other links and lift over

dbSNP: rs56282240; hg19: chr8-42977849;