8-43122619-C-T

Position:

chr8-43122619-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_032237.5(POMK):c.795C>T(p.Asp265Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0026 in 1,614,146 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 52 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 41 hom. )

Consequence

POMK
NM_032237.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.60

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]

POMK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 8-43122619-C-T is Benign according to our data. Variant chr8-43122619-C-T is described in ClinVar as [Benign]. Clinvar id is 382926.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.6 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0142 (2168/152274) while in subpopulation AFR AF= 0.0504 (2093/41538). AF 95% confidence interval is 0.0486. There are 52 homozygotes in gnomad4. There are 1059 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 52 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POMK	NM_032237.5 linkuse as main transcript	c.795C>T	p.Asp265Asp	synonymous_variant	5/5	ENST00000331373.10	NP_115613.1	Q9H5K3
POMK	NM_001277971.2 linkuse as main transcript	c.795C>T	p.Asp265Asp	synonymous_variant	4/4		NP_001264900.1	Q9H5K3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POMK	ENST00000331373.10 linkuse as main transcript	c.795C>T	p.Asp265Asp	synonymous_variant	5/5	2	NM_032237.5	ENSP00000331258.5		Q9H5K3

Frequencies

GnomAD3 genomes

AF:

0.0142

AC:

2164

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0505

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.00361

AC:

906

AN:

251312

Hom.:

AF XY:

0.00269

AC XY:

366

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.0519

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00138

AC:

2023

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

861

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0517

Gnomad4 AMR exome

AF:

0.00163

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000288

Gnomad4 OTH exome

AF:

0.00281

GnomAD4 genome

AF:

0.0142

AC:

2168

AN:

152274

Hom.:

Cov.:

AF XY:

0.0142

AC XY:

1059

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0504

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00946

Alfa

AF:

0.00626

Hom.:

Bravo

AF:

0.0153

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 04, 2016

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.8

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over