rs143726596

Variant names:

• chr16-66587063-C-G
• rs143726596
• NM_144673.3:c.511C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-66587063-C-G
• chr16-66587063-C-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.457

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]

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, 0.79

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMTM2	NM_144673.3	c.511C>G	p.Arg171Gly	missense_variant	Exon 3 of 4	ENST00000268595.3	NP_653274.1
CMTM2	NM_001199317.2	c.352C>G	p.Arg118Gly	missense_variant	Exon 2 of 3		NP_001186246.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CMTM2	ENST00000268595.3	c.511C>G	p.Arg171Gly	missense_variant	Exon 3 of 4	1	NM_144673.3	ENSP00000268595.2

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

Other links and lift over

dbSNP: rs143726596; hg19: chr16-66620966;