NM_032237.5:c.44G>C

Variant names:

• chr8-43103592-G-C
• NM_032237.5:c.44G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032237.5(POMK):​c.44G>C​(p.Arg15Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: POMK NM_032237.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.47

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38662812).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMK	NM_032237.5	c.44G>C	p.Arg15Pro	missense_variant	Exon 4 of 5	ENST00000331373.10	NP_115613.1
POMK	NM_001277971.2	c.44G>C	p.Arg15Pro	missense_variant	Exon 3 of 4		NP_001264900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMK	ENST00000331373.10	c.44G>C	p.Arg15Pro	missense_variant	Exon 4 of 5	2	NM_032237.5	ENSP00000331258.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461858 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727228

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0066	T;T;T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.065
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.52	T;T;.
M_CAP	Pathogenic	0.37	D
MetaRNN	Benign	0.39	T;T;T
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.3	M;.;M
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.99	.;N;N
REVEL	Uncertain	0.40
Sift	Uncertain	0.0040	.;D;D
Sift4G	Uncertain	0.0090	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.71
MutPred		0.52		Gain of catalytic residue at P14 (P = 0.0164);Gain of catalytic residue at P14 (P = 0.0164);Gain of catalytic residue at P14 (P = 0.0164);
MVP		0.79
MPC		0.47
ClinPred		0.81	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.32
gMVP		0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-42958735;