rs201220016

Variant names:

• chr9-131518922-C-A
• rs201220016
• NM_001077365.2:c.1451C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-131518922-C-A
• chr9-131518922-C-T

Variant summary

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

The NM_001077365.2(POMT1):​c.1451C>A​(p.Thr484Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,400 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: POMT1 NM_001077365.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.849

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]

ENSG00000230289 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMT1	NM_001077365.2	c.1451C>A	p.Thr484Lys	missense_variant	Exon 15 of 20	ENST00000402686.8	NP_001070833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMT1	ENST00000402686.8	c.1451C>A	p.Thr484Lys	missense_variant	Exon 15 of 20	1	NM_001077365.2	ENSP00000385797.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000160 AC: 4 AN: 250458 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135744

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461400 Hom.: 0 Cov.: 35 AF XY: 0.00000413 AC XY: 3 AN XY: 727006

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000113

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	17
DANN	Benign	0.68
DEOGEN2	Pathogenic	0.86	.;.;.;D;.;T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.81	T;T;T;T;.;T
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.71	D;D;D;D;D;D
MetaSVM	Uncertain	0.19	D
MutationAssessor	Pathogenic	2.9	.;.;.;M;.;.
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-3.2	D;D;D;D;D;D
REVEL	Uncertain	0.49
Sift	Benign	0.042	D;D;D;D;D;D
Sift4G	Benign	0.18	T;T;T;T;T;T
Polyphen		0.74, 0.22	.;P;.;B;P;.
Vest4		0.61
MutPred		0.75		.;.;.;Gain of methylation at T506 (P = 0.0041);.;.;
MVP		0.79
MPC		0.55
ClinPred		0.41	T
GERP RS		-7.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.32		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201220016; hg19: chr9-134394309;