rs4740165

Variant names:

• chr9-131522237-C-T
• rs4740165
• NM_001077365.2:c.2003+13C>T

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.2003+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.922 in 1,612,548 control chromosomes in the GnomAD database, including 689,255 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.85 (55947 hom., cov: 33)
  • Exomes 𝑓: 0.93 (633308 hom.)
• Consequence: POMT1 NM_001077365.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:14
• Conservation: PhyloP100: -1.60
• Publications: 15 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: Ambry Genetics, Laboratory for Molecular Medicine, Genomics England PanelApp, 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

ENSG00000230289 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 9-131522237-C-T is Benign according to our data. Variant chr9-131522237-C-T is described in ClinVar as Benign. ClinVar VariationId is 95460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.939 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.2003+13C>T		intron	N/A	NP_001070833.1	A0A140VKE0
	POMT1	NM_001353193.2		c.2069+13C>T		intron	N/A	NP_001340122.2	Q9Y6A1-1
	POMT1	NM_007171.4		c.2069+13C>T		intron	N/A	NP_009102.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMT1	ENST00000402686.8	TSL:1 MANE Select	c.2003+13C>T		intron	N/A	ENSP00000385797.4	Q9Y6A1-2
	POMT1	ENST00000372228.9	TSL:1	c.2069+13C>T		intron	N/A	ENSP00000361302.3	Q9Y6A1-1
	POMT1	ENST00000423007.6	TSL:1	c.2060+13C>T		intron	N/A	ENSP00000404119.2	A0A1V1FTP4

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128966 AN: 152100 Hom.: 55928 Cov.: 33

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.846

Gnomad ASJ AF: 0.923

Gnomad EAS AF: 0.917

Gnomad SAS AF: 0.962

Gnomad FIN AF: 0.934

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.938

Gnomad OTH AF: 0.864

GnomAD2 exomes AF: 0.902 AC: 225334 AN: 249940 AF XY: 0.912

Gnomad AFR exome AF: 0.636

Gnomad AMR exome AF: 0.829

Gnomad ASJ exome AF: 0.925

Gnomad EAS exome AF: 0.914

Gnomad FIN exome AF: 0.932

Gnomad NFE exome AF: 0.935

Gnomad OTH exome AF: 0.913

GnomAD4 exome AF: 0.930 AC: 1357755 AN: 1460330 Hom.: 633308 Cov.: 76 AF XY: 0.932 AC XY: 676988 AN XY: 726600

African (AFR) AF: 0.633 AC: 21208 AN: 33480

American (AMR) AF: 0.830 AC: 37111 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.925 AC: 24177 AN: 26136

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

South Asian (SAS) AF: 0.962 AC: 82961 AN: 86256

European-Finnish (FIN) AF: 0.931 AC: 48322 AN: 51918

Middle Eastern (MID) AF: 0.913 AC: 5268 AN: 5768

European-Non Finnish (NFE) AF: 0.942 AC: 1047447 AN: 1111980

Other (OTH) AF: 0.909 AC: 54887 AN: 60382

GnomAD4 genome AF: 0.848 AC: 129020 AN: 152218 Hom.: 55947 Cov.: 33 AF XY: 0.850 AC XY: 63258 AN XY: 74436

African (AFR) AF: 0.647 AC: 26868 AN: 41498

American (AMR) AF: 0.846 AC: 12945 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.923 AC: 3202 AN: 3470

East Asian (EAS) AF: 0.917 AC: 4739 AN: 5166

South Asian (SAS) AF: 0.962 AC: 4645 AN: 4826

European-Finnish (FIN) AF: 0.934 AC: 9918 AN: 10614

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.938 AC: 63800 AN: 68028

Other (OTH) AF: 0.865 AC: 1827 AN: 2112

Alfa AF: 0.902 Hom.: 74086

Bravo AF: 0.829

Asia WGS AF: 0.890 AC: 3092 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	7	not specified (7)
-	-	2	Autosomal recessive limb-girdle muscular dystrophy type 2K (2)
-	-	2	not provided (2)
-	-	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	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	-0.89
CADD	Benign	1.0
DANN	Benign	0.51
PhyloP100		-1.6
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: rs4740165; hg19: chr9-134397624;