Genetic Variant CLMP:p.Arg168Gln (chr11-123083733-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024769.5(CLMP):c.503G>A(p.Arg168Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000155 in 1,613,934 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

CLMP
NM_024769.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.75

Publications

1 publications found

Variant links:

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]

CLMP Gene-Disease associations (from GenCC):

congenital short bowel syndrome, autosomal recessive
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
congenital short bowel syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CLMP links:

LOC124902775 (HGNC:):

LOC124902775 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024769.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLMP	NM_024769.5	MANE Select	c.503G>A	p.Arg168Gln	missense	Exon 4 of 7	NP_079045.1	Q9H6B4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLMP	ENST00000448775.4	TSL:1 MANE Select	c.503G>A	p.Arg168Gln	missense	Exon 4 of 7	ENSP00000405577.2	Q9H6B4
CLMP	ENST00000950922.1		c.518G>A	p.Arg173Gln	missense	Exon 4 of 7	ENSP00000620981.1
CLMP	ENST00000715744.1		c.503G>A	p.Arg168Gln	missense	Exon 4 of 7	ENSP00000520511.1	Q9H6B4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000119

AC:

AN:

251460

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1461828

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727210

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.0000374

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.0000180

AC:

AN:

1112000

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41420

American (AMR)

AF:

0.00

AC:

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.030

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.021

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.80

M_CAP

Benign

0.031

MetaRNN

Uncertain

0.72

MetaSVM

Benign

-0.84

MutationAssessor

Pathogenic

3.0

PhyloP100

4.8

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.8

REVEL

Benign

0.28

Sift

Benign

0.067

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.72

MutPred

0.39

Gain of methylation at K172 (P = 0.0643)

MVP

0.42

MPC

1.1

ClinPred

0.93

GERP RS

5.5

Varity_R

0.66

gMVP

0.85

Mutation Taster

=66/34

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over