9-131515443-CCCT-C

Variant names:

• chr9-131515443-CCCT-C
• rs587777818
• NM_001077365.2:c.1194_1196delCCT

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM1 PM2 PM4_Supporting PP5

The NM_001077365.2(POMT1):​c.1194_1196delCCT​(p.Leu399del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. P398P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: POMT1 NM_001077365.2 disruptive_inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.41
• Publications: 0 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM1: In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 9 uncertain in NM_001077365.2
• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001077365.2. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 9-131515443-CCCT-C is Pathogenic according to our data. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-131515443-CCCT-C is described in CliVar as Pathogenic. Clinvar id is 3241.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMT1	NM_001077365.2	c.1194_1196delCCT	p.Leu399del	disruptive_inframe_deletion	Exon 13 of 20	ENST00000402686.8	NP_001070833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMT1	ENST00000402686.8	c.1194_1196delCCT	p.Leu399del	disruptive_inframe_deletion	Exon 13 of 20	1	NM_001077365.2	ENSP00000385797.4

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

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

Mar 23, 2004

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.4
Mutation Taster		=51/49	disease causing (ClinVar)

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: rs587777818; hg19: chr9-134390830;