9-131506184-G-C

Variant names:

• chr9-131506184-G-C
• NM_001077365.2:c.193G>C

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PS1 PM2 PP3_Strong

The NM_001077365.2(POMT1):​c.193G>C​(p.Gly65Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Pathogenic in Lovd.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: POMT1 NM_001077365.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.36

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 Pathogenic. Variant got 10 ACMG points.

• PS1: Transcript NM_001077365.2 (POMT1) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in Lovd
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.964

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMT1	NM_001077365.2	c.193G>C	p.Gly65Arg	missense_variant	Exon 3 of 20	ENST00000402686.8	NP_001070833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMT1	ENST00000402686.8	c.193G>C	p.Gly65Arg	missense_variant	Exon 3 of 20	1	NM_001077365.2	ENSP00000385797.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461884 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

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: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.41	.;.;T;.;T;T
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D;D;.;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.96	D;D;D;D;D;D
MetaSVM	Uncertain	0.28	D
MutationAssessor	Uncertain	2.4	M;.;M;M;.;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.0	N;N;N;N;N;N
REVEL	Pathogenic	0.72
Sift	Benign	0.22	T;T;T;T;T;T
Sift4G	Benign	0.13	T;T;T;T;D;D
Polyphen		1.0	D;.;D;D;.;.
Vest4		0.97
MutPred		0.94		Loss of glycosylation at S64 (P = 0.0503);.;Loss of glycosylation at S64 (P = 0.0503);Loss of glycosylation at S64 (P = 0.0503);Loss of glycosylation at S64 (P = 0.0503);.;
MVP		0.93
MPC		0.98
ClinPred		0.91	D
GERP RS		5.7
Varity_R		0.79
gMVP		0.97

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: chr9-134381571;