chr11-123084669-CT-C

Position:

• chr11-123084669-CT-C

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_024769.5(CLMP):​c.230del​(p.Glu77GlyfsTer25) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLMP NM_024769.5 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.00

Genes affected

CLMP (HGNC:24039): (CXADR like membrane protein) This gene encodes a type I transmembrane protein that is localized to junctional complexes between endothelial and epithelial cells and may have a role in cell-cell adhesion. Expression of this gene in white adipose tissue is implicated in adipocyte maturation and development of obesity. This gene is also essential for normal intestinal development and mutations in the gene are associated with congenital short bowel syndrome. [provided by RefSeq, Aug 2015]

(HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 11-123084669-CT-C is Pathogenic according to our data. Variant chr11-123084669-CT-C is described in ClinVar as [Pathogenic]. Clinvar id is 50383.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLMP	NM_024769.5	c.230del	p.Glu77GlyfsTer25	frameshift_variant	3/7	ENST00000448775.4	NP_079045.1
LOC124902775	XR_007062927.1	n.2527del		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLMP	ENST00000448775.4	c.230del	p.Glu77GlyfsTer25	frameshift_variant	3/7	1	NM_024769.5	ENSP00000405577	P1
	ENST00000660892.2	n.524del		non_coding_transcript_exon_variant	3/3
CLMP	ENST00000527977.5	n.45del		non_coding_transcript_exon_variant	1/5	3
CLMP	ENST00000529128.1	n.216del		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Congenital short bowel syndrome, autosomal recessive Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 01, 2012

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs587776964; hg19: chr11-122955377;