11-123083097-C-A

Variant names:

• chr11-123083097-C-A
• rs901336794
• NM_024769.5:c.667G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024769.5(CLMP):​c.667G>T​(p.Val223Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CLMP NM_024769.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.95

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]

LOC124902775 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLMP	NM_024769.5	c.667G>T	p.Val223Leu	missense_variant	Exon 5 of 7	ENST00000448775.4	NP_079045.1
LOC124902775	XR_007062927.1	n.954C>A		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLMP	ENST00000448775.4	c.667G>T	p.Val223Leu	missense_variant	Exon 5 of 7	1	NM_024769.5	ENSP00000405577.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251354 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135834

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461874 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727236

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.27
Sift	Benign	0.40	T
Sift4G	Uncertain	0.012	D
Polyphen		0.99	D
Vest4		0.64
MutPred		0.46		Loss of MoRF binding (P = 0.2818);
MVP		0.24
MPC		0.73
ClinPred		0.88	D
GERP RS		5.4
Varity_R		0.21
gMVP		0.64

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: rs901336794; hg19: chr11-122953805;