rs1064793740

Variant names:

• chr9-131522040-CC-AA
• rs1064793740
• NM_001077365.2:c.1826-7_1826-6delCCinsAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_001077365.2(POMT1):​c.1826-7_1826-6delCCinsAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: POMT1 NM_001077365.2 splice_region, intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.352
• 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

ENSG00000230289 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP6: Variant 9-131522040-CC-AA is Benign according to our data. Variant chr9-131522040-CC-AA is described in ClinVar as Likely_benign. ClinVar VariationId is 419235.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMT1	NM_001077365.2	MANE Select	c.1826-7_1826-6delCCinsAA		splice_region intron	N/A	NP_001070833.1
	POMT1	NM_001353193.2		c.1892-7_1892-6delCCinsAA		splice_region intron	N/A	NP_001340122.2
	POMT1	NM_007171.4		c.1892-7_1892-6delCCinsAA		splice_region intron	N/A	NP_009102.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMT1	ENST00000402686.8	TSL:1 MANE Select	c.1826-7_1826-6delCCinsAA		splice_region intron	N/A	ENSP00000385797.4
	POMT1	ENST00000372228.9	TSL:1	c.1892-7_1892-6delCCinsAA		splice_region intron	N/A	ENSP00000361302.3
	POMT1	ENST00000423007.6	TSL:1	c.1883-7_1883-6delCCinsAA		splice_region intron	N/A	ENSP00000404119.2

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

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (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
PhyloP100		0.35

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1064793740; hg19: chr9-134397427;