9-131509995-A-T

Variant names:

• chr9-131509995-A-T
• rs139774354
• ENST00000372228.9:c.698A>T

Variant summary

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

The NM_001411024.1(POMT1):​c.-439A>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.0000031 in 1,613,988 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: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: POMT1 NM_001411024.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.01

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30396155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMT1	NM_001077365.2	c.698A>T	p.Asn233Ile	missense_variant, splice_region_variant	Exon 8 of 20	ENST00000402686.8	NP_001070833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMT1	ENST00000402686.8	c.698A>T	p.Asn233Ile	missense_variant, splice_region_variant	Exon 8 of 20	1	NM_001077365.2	ENSP00000385797.4

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152176 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461812 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727208

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: 0.00

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152176 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74334

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000478

Bravo AF: 0.0000340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.50	.;.;T;.;D;.;T;.
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.76	D
LIST_S2	Uncertain	0.87	D;D;T;D;T;.;T;D
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.30	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	0.81	.;L;.;.;L;L;.;.
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-4.7	D;D;D;D;D;D;D;D
REVEL	Benign	0.28
Sift	Benign	0.060	T;T;D;T;D;T;D;T
Sift4G	Benign	0.11	T;T;D;T;D;T;D;T
Polyphen		0.071, 0.63	.;B;.;.;P;B;.;.
Vest4		0.72
MutPred		0.41		.;Gain of helix (P = 0.0425);.;.;Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);.;.;
MVP		0.82
MPC		0.85
ClinPred		0.98	D
GERP RS		3.2
Varity_R		0.52
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs139774354; hg19: chr9-134385382;