rs2296949

Positions:

• chr9-131510049-A-C
• chr9-131510049-A-G
• chr9-131510049-A-T

Variant summary

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

The ENST00000372228.9(POMT1):​c.752A>C​(p.Gln251Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 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. Q251R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: POMT1 ENST00000372228.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.989

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=0.20950502).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMT1	NM_001077365.2	c.699+53A>C		intron_variant		ENST00000402686.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMT1	ENST00000402686.8	c.699+53A>C		intron_variant		1	NM_001077365.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 83

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	1.4
DANN	Benign	0.18
DEOGEN2	Benign	0.18	T;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.19	T;T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.85	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.24	N;N;N
REVEL	Benign	0.23
Sift	Benign	0.33	T;T;T
Sift4G	Benign	0.24	T;T;T
Polyphen		0.0010	.;B;.
Vest4		0.13
MutPred		0.68		.;Gain of glycosylation at Q251 (P = 0.0297);.;
MVP		0.65
MPC		0.30
ClinPred		0.15	T
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.035
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2296949; hg19: chr9-134385436;