rs886044651

Variant names:

• chr9-131506142-A-C
• NM_001077365.2:c.151A>C

Your query was ambiguous. Multiple possible variants found:

• chr9-131506142-A-C
• chr9-131506142-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_001077365.2(POMT1):​c.151A>C​(p.Ile51Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. 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.

• 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: 1.43

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 3 ACMG points.

• PM1: In a transmembrane_region Helical (size 20) in uniprot entity POMT1_HUMAN there are 7 pathogenic changes around while only 1 benign (88%) in NM_001077365.2
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3275742).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMT1	NM_001077365.2	c.151A>C	p.Ile51Leu	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.151A>C	p.Ile51Leu	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: 1461880 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727238

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	Benign	0.14
BayesDel_addAF	Benign	-0.0068	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Uncertain	0.45	.;T;.;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.82	T;T;.;T
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.33	T;T;T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	1.0	L;L;L;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.2	N;N;N;N
REVEL	Benign	0.20
Sift	Benign	0.15	T;T;T;T
Sift4G	Benign	0.20	T;T;T;T
Polyphen		0.0010	B;B;B;.
Vest4		0.36
MutPred		0.57		Loss of catalytic residue at I51 (P = 0.0769);Loss of catalytic residue at I51 (P = 0.0769);Loss of catalytic residue at I51 (P = 0.0769);Loss of catalytic residue at I51 (P = 0.0769);
MVP		0.64
MPC		0.26
ClinPred		0.25	T
GERP RS		3.1
Varity_R		0.13
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr9-134381529;