rs3739494

Variant names:

• chr9-131512101-T-C
• rs3739494
• NM_001077365.2:c.1047T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-131512101-T-C
• chr9-131512101-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001077365.2(POMT1):​c.1047T>C​(p.Asp349Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.94 in 1,613,944 control chromosomes in the GnomAD database, including 714,925 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.89 (60599 hom., cov: 31)
  • Exomes 𝑓: 0.95 (654326 hom.)
• Consequence: POMT1 NM_001077365.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -1.54
• Publications: 33 publications found

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]

POMT1 Gene-Disease associations (from GenCC):

• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Laboratory for Molecular Medicine, Ambry Genetics, G2P
• myopathy caused by variation in POMT1

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• autosomal recessive limb-girdle muscular dystrophy type 2K

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• congenital muscular dystrophy with cerebellar involvement

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• congenital muscular dystrophy with intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• congenital muscular dystrophy without intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• muscle-eye-brain disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• muscular dystrophy-dystroglycanopathy, type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 9-131512101-T-C is Benign according to our data. Variant chr9-131512101-T-C is described in ClinVar as Benign. ClinVar VariationId is 167520.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.54 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077365.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMT1	NM_001077365.2	MANE Select	c.1047T>C	p.Asp349Asp	synonymous	Exon 11 of 20	NP_001070833.1	A0A140VKE0
	POMT1	NM_001353193.2		c.1113T>C	p.Asp371Asp	synonymous	Exon 11 of 20	NP_001340122.2	Q9Y6A1-1
	POMT1	NM_007171.4		c.1113T>C	p.Asp371Asp	synonymous	Exon 11 of 20	NP_009102.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMT1	ENST00000402686.8	TSL:1 MANE Select	c.1047T>C	p.Asp349Asp	synonymous	Exon 11 of 20	ENSP00000385797.4	Q9Y6A1-2
	POMT1	ENST00000372228.9	TSL:1	c.1113T>C	p.Asp371Asp	synonymous	Exon 11 of 20	ENSP00000361302.3	Q9Y6A1-1
	POMT1	ENST00000423007.6	TSL:1	c.1104T>C	p.Asp368Asp	synonymous	Exon 10 of 19	ENSP00000404119.2	A0A1V1FTP4

Frequencies

GnomAD3 genomes AF: 0.888 AC: 134901 AN: 151990 Hom.: 60568 Cov.: 31

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.899

Gnomad AMR AF: 0.861

Gnomad ASJ AF: 0.941

Gnomad EAS AF: 0.918

Gnomad SAS AF: 0.970

Gnomad FIN AF: 0.978

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.954

Gnomad OTH AF: 0.895

GnomAD2 exomes AF: 0.924 AC: 232202 AN: 251354 AF XY: 0.932

Gnomad AFR exome AF: 0.735

Gnomad AMR exome AF: 0.841

Gnomad ASJ exome AF: 0.943

Gnomad EAS exome AF: 0.914

Gnomad FIN exome AF: 0.977

Gnomad NFE exome AF: 0.953

Gnomad OTH exome AF: 0.931

GnomAD4 exome AF: 0.945 AC: 1381715 AN: 1461836 Hom.: 654326 Cov.: 94 AF XY: 0.947 AC XY: 688653 AN XY: 727208

African (AFR) AF: 0.732 AC: 24520 AN: 33480

American (AMR) AF: 0.842 AC: 37654 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.942 AC: 24632 AN: 26136

East Asian (EAS) AF: 0.916 AC: 36374 AN: 39698

South Asian (SAS) AF: 0.971 AC: 83704 AN: 86244

European-Finnish (FIN) AF: 0.976 AC: 52144 AN: 53414

Middle Eastern (MID) AF: 0.936 AC: 5399 AN: 5768

European-Non Finnish (NFE) AF: 0.954 AC: 1061248 AN: 1111994

Other (OTH) AF: 0.928 AC: 56040 AN: 60396

GnomAD4 genome AF: 0.887 AC: 134974 AN: 152108 Hom.: 60599 Cov.: 31 AF XY: 0.889 AC XY: 66130 AN XY: 74372

African (AFR) AF: 0.746 AC: 30904 AN: 41450

American (AMR) AF: 0.861 AC: 13166 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.941 AC: 3267 AN: 3470

East Asian (EAS) AF: 0.918 AC: 4732 AN: 5154

South Asian (SAS) AF: 0.971 AC: 4680 AN: 4822

European-Finnish (FIN) AF: 0.978 AC: 10373 AN: 10608

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.954 AC: 64869 AN: 68002

Other (OTH) AF: 0.897 AC: 1894 AN: 2112

Alfa AF: 0.930 Hom.: 128788

Bravo AF: 0.869

Asia WGS AF: 0.917 AC: 3189 AN: 3478

EpiCase AF: 0.949

EpiControl AF: 0.947

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	1	Autosomal recessive limb-girdle muscular dystrophy type 2K (1)
-	-	1	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 (1)
-	-	1	Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 (1)
-	-	1	not provided (1)
-	-	1	Walker-Warburg congenital muscular dystrophy;C1836373:Autosomal recessive limb-girdle muscular dystrophy type 2K;C5436962:Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.49
DANN	Benign	0.67
PhyloP100		-1.5
Mutation Taster		=94/6	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3739494; hg19: chr9-134387488; COSMIC: COSV108169146; COSMIC: COSV108169146;