rs143726596

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_144673.3(CMTM2):​c.511C>G​(p.Arg171Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R171W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

CMTM2
NM_144673.3 missense

Scores

2
4
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.457
Variant links:
Genes affected
CMTM2 (HGNC:19173): (CKLF like MARVEL transmembrane domain containing 2) This gene belongs to the chemokine-like factor gene superfamily, a novel family that links the chemokine and the transmembrane 4 superfamilies of signaling molecules. The protein encoded by this gene may play an important role in testicular development. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

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, 0.79

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CMTM2NM_144673.3 linkc.511C>G p.Arg171Gly missense_variant Exon 3 of 4 ENST00000268595.3 NP_653274.1 Q8TAZ6-1
CMTM2NM_001199317.2 linkc.352C>G p.Arg118Gly missense_variant Exon 2 of 3 NP_001186246.1 Q8TAZ6-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CMTM2ENST00000268595.3 linkc.511C>G p.Arg171Gly missense_variant Exon 3 of 4 1 NM_144673.3 ENSP00000268595.2 Q8TAZ6-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
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
Uncertain
0.38
BayesDel_addAF
Benign
-0.091
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
14
DANN
Benign
0.91
DEOGEN2
Benign
0.073
.;T
Eigen
Benign
-0.41
Eigen_PC
Benign
-0.66
FATHMM_MKL
Benign
0.029
N
LIST_S2
Benign
0.51
T;T
M_CAP
Benign
0.013
T
MetaRNN
Pathogenic
0.79
D;D
MetaSVM
Benign
-0.95
T
MutationAssessor
Uncertain
2.0
.;M
PrimateAI
Benign
0.29
T
PROVEAN
Pathogenic
-4.9
D;D
REVEL
Benign
0.16
Sift
Uncertain
0.028
D;D
Sift4G
Uncertain
0.028
D;D
Polyphen
1.0
.;D
Vest4
0.55
MutPred
0.70
.;Loss of methylation at R171 (P = 0.0414);
MVP
0.56
MPC
0.59
ClinPred
0.93
D
GERP RS
0.85
Varity_R
0.28
gMVP
0.46

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs143726596; hg19: chr16-66620966; API