11-123074795-G-T

Variant names:

• chr11-123074795-G-T
• rs369507357
• NM_024769.5:c.728C>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_024769.5(CLMP):​c.728C>A​(p.Ala243Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLMP NM_024769.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.92

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]

ENSG00000288061 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.815

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLMP	NM_024769.5	c.728C>A	p.Ala243Asp	missense_variant	Exon 6 of 7	ENST00000448775.4	NP_079045.1
LOC124902775	XR_007062927.1	n.871-8219G>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLMP	ENST00000448775.4	c.728C>A	p.Ala243Asp	missense_variant	Exon 6 of 7	1	NM_024769.5	ENSP00000405577.2
CLMP	ENST00000527977.5	n.550C>A		non_coding_transcript_exon_variant	Exon 4 of 5	3
CLMP	ENST00000530371.5	n.202C>A		non_coding_transcript_exon_variant	Exon 3 of 4	4
ENSG00000288061	ENST00000660892.2	n.227-9578G>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.061	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Uncertain	-0.011	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.5	N
REVEL	Uncertain	0.49
Sift	Uncertain	0.021	D
Sift4G	Benign	0.098	T
Polyphen		0.94	P
Vest4		0.89
MutPred		0.58		Gain of loop (P = 0.0435);
MVP		0.91
MPC		1.2
ClinPred		0.97	D
GERP RS		5.3
Varity_R		0.27
gMVP		0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs369507357; hg19: chr11-122945503;