9-131510212-A-G

Variant names:

• chr9-131510212-A-G
• rs2018621
• NM_001077365.2:c.700-48A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001077365.2(POMT1):​c.700-48A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.94 in 1,613,422 control chromosomes in the GnomAD database, including 714,691 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.89 (60678 hom., cov: 35)
  • Exomes 𝑓: 0.95 (654013 hom.)
• Consequence: POMT1 NM_001077365.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -3.21
• Publications: 14 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: G2P, Ambry Genetics, Laboratory for Molecular Medicine, Genomics England PanelApp
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 9-131510212-A-G is Benign according to our data. Variant chr9-131510212-A-G is described in ClinVar as Benign. ClinVar VariationId is 260151.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMT1	NM_001077365.2	c.700-48A>G		intron_variant	Intron 8 of 19	ENST00000402686.8	NP_001070833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMT1	ENST00000402686.8	c.700-48A>G		intron_variant	Intron 8 of 19	1	NM_001077365.2	ENSP00000385797.4

Frequencies

GnomAD3 genomes AF: 0.887 AC: 135088 AN: 152218 Hom.: 60647 Cov.: 35

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.899

Gnomad AMR AF: 0.861

Gnomad ASJ AF: 0.942

Gnomad EAS AF: 0.917

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: 230289 AN: 249282 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: 1381040 AN: 1461086 Hom.: 654013 Cov.: 66 AF XY: 0.947 AC XY: 688273 AN XY: 726794

African (AFR) AF: 0.732 AC: 24512 AN: 33468

American (AMR) AF: 0.842 AC: 37486 AN: 44508

Ashkenazi Jewish (ASJ) AF: 0.942 AC: 24614 AN: 26118

East Asian (EAS) AF: 0.916 AC: 36369 AN: 39692

South Asian (SAS) AF: 0.971 AC: 83622 AN: 86156

European-Finnish (FIN) AF: 0.976 AC: 52104 AN: 53372

Middle Eastern (MID) AF: 0.936 AC: 5398 AN: 5766

European-Non Finnish (NFE) AF: 0.954 AC: 1060922 AN: 1111642

Other (OTH) AF: 0.928 AC: 56013 AN: 60364

GnomAD4 genome AF: 0.887 AC: 135161 AN: 152336 Hom.: 60678 Cov.: 35 AF XY: 0.889 AC XY: 66248 AN XY: 74502

African (AFR) AF: 0.746 AC: 30984 AN: 41556

American (AMR) AF: 0.861 AC: 13184 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.942 AC: 3269 AN: 3472

East Asian (EAS) AF: 0.917 AC: 4758 AN: 5186

South Asian (SAS) AF: 0.971 AC: 4690 AN: 4832

European-Finnish (FIN) AF: 0.978 AC: 10388 AN: 10626

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

European-Non Finnish (NFE) AF: 0.954 AC: 64902 AN: 68038

Other (OTH) AF: 0.897 AC: 1897 AN: 2116

Alfa AF: 0.936 Hom.: 35872

Bravo AF: 0.869

Asia WGS AF: 0.917 AC: 3189 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive limb-girdle muscular dystrophy type 2K Benign:1

Oct 25, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 Benign:1

Oct 25, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 Benign:1

Oct 25, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.071
DANN	Benign	0.31
PhyloP100		-3.2
PromoterAI		-0.0052	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	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: rs2018621; hg19: chr9-134385599;