9-131508971-A-T

Position:

• chr9-131508971-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001077365.2(POMT1):​c.488A>T​(p.Asn163Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N163S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: POMT1 NM_001077365.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.70

Genes affected

POMT1 (HGNC:9202): (protein O-mannosyltransferase 1) The protein encoded by this gene is an O-mannosyltransferase that requires interaction with the product of the POMT2 gene for enzymatic function. The encoded protein is found in the membrane of the endoplasmic reticulum. Defects in this gene are a cause of Walker-Warburg syndrome (WWS) and limb-girdle muscular dystrophy type 2K (LGMD2K). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18382162).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMT1	NM_001077365.2	c.488A>T	p.Asn163Ile	missense_variant	6/20	ENST00000402686.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMT1	ENST00000402686.8	c.488A>T	p.Asn163Ile	missense_variant	6/20	1	NM_001077365.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461752 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727188

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: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.21	.;.;T;.;T;.;T;T;.
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.058
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.88	D;D;D;D;D;.;D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.18	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	-1.1	.;N;.;.;N;N;.;.;.
MutationTaster	Benign	1.0	D;N;N;N;N;N;N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.1	N;N;N;N;N;N;N;N;N
REVEL	Benign	0.27
Sift	Benign	0.13	T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.56	T;T;T;T;T;T;T;T;T
Polyphen		0.0, 0.0020	.;B;.;.;B;B;.;.;.
Vest4		0.46
MutPred		0.62		.;Loss of catalytic residue at N163 (P = 0.1001);.;.;Loss of catalytic residue at N163 (P = 0.1001);Loss of catalytic residue at N163 (P = 0.1001);.;.;.;
MVP		0.87
MPC		0.33
ClinPred		0.54	D
GERP RS		5.6
Varity_R		0.16
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs182295674; hg19: chr9-134384358;