Variant 8-43103459-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_032237.5(POMK):c.-21-69A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00903 in 1,469,466 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0082 ( 12 hom., cov: 32)

Exomes 𝑓: 0.0091 ( 85 hom. )

Consequence

POMK
NM_032237.5 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0470

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 8-43103459-A-G is Benign according to our data. Variant chr8-43103459-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1215652.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00822 (1251/152270) while in subpopulation NFE AF= 0.00875 (595/68006). AF 95% confidence interval is 0.00817. There are 12 homozygotes in gnomad4. There are 691 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMK	NM_032237.5 linkuse as main transcript	c.-21-69A>G		intron_variant		ENST00000331373.10
POMK	NM_001277971.2 linkuse as main transcript	c.-21-69A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMK	ENST00000331373.10 linkuse as main transcript	c.-21-69A>G		intron_variant		2	NM_032237.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00823

AC:

1252

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00668

Gnomad ASJ

AF:

0.0190

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00456

Gnomad FIN

AF:

0.0374

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00876

Gnomad OTH

AF:

0.00669

GnomAD4 exome

AF:

0.00912

AC:

12019

AN:

1317196

Hom.:

AF XY:

0.00921

AC XY:

6050

AN XY:

656940

show subpopulations

Gnomad4 AFR exome

AF:

0.00142

Gnomad4 AMR exome

AF:

0.00444

Gnomad4 ASJ exome

AF:

0.0201

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00458

Gnomad4 FIN exome

AF:

0.0307

Gnomad4 NFE exome

AF:

0.00883

Gnomad4 OTH exome

AF:

0.00909

GnomAD4 genome

AF:

0.00822

AC:

1251

AN:

152270

Hom.:

Cov.:

AF XY:

0.00928

AC XY:

691

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.00667

Gnomad4 ASJ

AF:

0.0190

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.0374

Gnomad4 NFE

AF:

0.00875

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00935

Hom.:

Bravo

AF:

0.00615

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.97

DANN

Benign

0.25

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