rs10901066

Variant names:

• chr9-131511516-G-A
• rs10901066
• NM_001077365.2:c.986+49G>A

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.986+49G>A 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 1,609,874 control chromosomes in the GnomAD database, including 713,176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.89 (60671 hom., cov: 33)
  • Exomes 𝑓: 0.95 (652505 hom.)
• Consequence: POMT1 NM_001077365.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.454
• Publications: 13 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=-0.96).
• BP6: Variant 9-131511516-G-A is Benign according to our data. Variant chr9-131511516-G-A is described in ClinVar as Benign. ClinVar VariationId is 260139.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.986+49G>A		intron_variant	Intron 10 of 19	ENST00000402686.8	NP_001070833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMT1	ENST00000402686.8	c.986+49G>A		intron_variant	Intron 10 of 19	1	NM_001077365.2	ENSP00000385797.4

Frequencies

GnomAD3 genomes AF: 0.888 AC: 135076 AN: 152182 Hom.: 60640 Cov.: 33

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.899

Gnomad AMR AF: 0.861

Gnomad ASJ AF: 0.942

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: 231997 AN: 251130 AF XY: 0.932

Gnomad AFR exome AF: 0.735

Gnomad AMR exome AF: 0.842

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: 1377774 AN: 1457574 Hom.: 652505 Cov.: 32 AF XY: 0.947 AC XY: 687027 AN XY: 725444

African (AFR) AF: 0.733 AC: 24454 AN: 33380

American (AMR) AF: 0.843 AC: 37645 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.943 AC: 24610 AN: 26110

East Asian (EAS) AF: 0.916 AC: 36353 AN: 39668

South Asian (SAS) AF: 0.971 AC: 83551 AN: 86086

European-Finnish (FIN) AF: 0.976 AC: 51970 AN: 53234

Middle Eastern (MID) AF: 0.936 AC: 5325 AN: 5690

European-Non Finnish (NFE) AF: 0.954 AC: 1057946 AN: 1108472

Other (OTH) AF: 0.928 AC: 55920 AN: 60254

GnomAD4 genome AF: 0.887 AC: 135149 AN: 152300 Hom.: 60671 Cov.: 33 AF XY: 0.889 AC XY: 66232 AN XY: 74478

African (AFR) AF: 0.746 AC: 30966 AN: 41516

American (AMR) AF: 0.861 AC: 13187 AN: 15310

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

East Asian (EAS) AF: 0.918 AC: 4758 AN: 5184

South Asian (SAS) AF: 0.971 AC: 4692 AN: 4834

European-Finnish (FIN) AF: 0.978 AC: 10383 AN: 10620

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

European-Non Finnish (NFE) AF: 0.954 AC: 64908 AN: 68042

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

Alfa AF: 0.915 Hom.: 13518

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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. -

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	-0.96
CADD	Benign	0.31
DANN	Benign	0.36
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10901066; hg19: chr9-134386903;