NM_001077365.2:c.428-21T>C

Variant names:

• chr9-131508890-T-C
• rs11243404
• NM_001077365.2:c.428-21T>C

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.428-21T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.939 in 1,548,266 control chromosomes in the GnomAD database, including 685,522 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.89 (60646 hom., cov: 32)
  • Exomes 𝑓: 0.95 (624876 hom.)
• Consequence: POMT1 NM_001077365.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.677
• Publications: 10 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 9-131508890-T-C is Benign according to our data. Variant chr9-131508890-T-C is described in ClinVar as Benign. ClinVar VariationId is 260149.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.

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.428-21T>C		intron	N/A	NP_001070833.1
	POMT1	NM_001353193.2		c.428-21T>C		intron	N/A	NP_001340122.2
	POMT1	NM_007171.4		c.428-21T>C		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.428-21T>C		intron	N/A	ENSP00000385797.4
	POMT1	ENST00000372228.9	TSL:1	c.428-21T>C		intron	N/A	ENSP00000361302.3
	POMT1	ENST00000423007.6	TSL:1	c.419-21T>C		intron	N/A	ENSP00000404119.2

Frequencies

GnomAD3 genomes AF: 0.888 AC: 135015 AN: 152128 Hom.: 60614 Cov.: 32

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: 232117 AN: 251232 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: 1319473 AN: 1396020 Hom.: 624876 Cov.: 22 AF XY: 0.947 AC XY: 661372 AN XY: 698324

African (AFR) AF: 0.734 AC: 23505 AN: 32030

American (AMR) AF: 0.842 AC: 37563 AN: 44586

Ashkenazi Jewish (ASJ) AF: 0.942 AC: 24260 AN: 25742

East Asian (EAS) AF: 0.916 AC: 36080 AN: 39372

South Asian (SAS) AF: 0.971 AC: 82408 AN: 84898

European-Finnish (FIN) AF: 0.976 AC: 52074 AN: 53340

Middle Eastern (MID) AF: 0.937 AC: 5294 AN: 5650

European-Non Finnish (NFE) AF: 0.954 AC: 1004353 AN: 1052258

Other (OTH) AF: 0.928 AC: 53936 AN: 58144

GnomAD4 genome AF: 0.887 AC: 135089 AN: 152246 Hom.: 60646 Cov.: 32 AF XY: 0.889 AC XY: 66208 AN XY: 74450

African (AFR) AF: 0.746 AC: 30941 AN: 41502

American (AMR) AF: 0.861 AC: 13171 AN: 15290

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

East Asian (EAS) AF: 0.918 AC: 4757 AN: 5182

South Asian (SAS) AF: 0.971 AC: 4686 AN: 4828

European-Finnish (FIN) AF: 0.978 AC: 10381 AN: 10618

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

European-Non Finnish (NFE) AF: 0.954 AC: 64899 AN: 68034

Other (OTH) AF: 0.897 AC: 1896 AN: 2114

Alfa AF: 0.920 Hom.: 12377

Bravo AF: 0.869

Asia WGS AF: 0.917 AC: 3188 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	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	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	-0.96
CADD	Benign	0.087
DANN	Benign	0.32
PhyloP100		-0.68
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: rs11243404; hg19: chr9-134384277;