rs1371116420

Variant names:

• chr16-66579815-C-G
• rs1371116420
• NM_144673.3:c.208C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-66579815-C-G
• chr16-66579815-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_144673.3(CMTM2):​c.208C>G​(p.Arg70Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: CMTM2 NM_144673.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

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]

ENSG00000260650 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28424942).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMTM2	NM_144673.3	c.208C>G	p.Arg70Gly	missense_variant	Exon 1 of 4	ENST00000268595.3	NP_653274.1
CMTM2	NM_001199317.2	c.208C>G	p.Arg70Gly	missense_variant	Exon 1 of 3		NP_001186246.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CMTM2	ENST00000268595.3	c.208C>G	p.Arg70Gly	missense_variant	Exon 1 of 4	1	NM_144673.3	ENSP00000268595.2
CMTM2	ENST00000379486.6	c.208C>G	p.Arg70Gly	missense_variant	Exon 1 of 3	1		ENSP00000368800.2
CMTM2	ENST00000569316.1	n.91+117C>G		intron_variant	Intron 1 of 3	5		ENSP00000454319.1
ENSG00000260650	ENST00000568430.1	n.*168G>C		downstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151936 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151936 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74208

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.0016	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.068	.;T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;L
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-4.5	D;D
REVEL	Benign	0.15
Sift	Benign	0.28	T;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.86	.;P
Vest4		0.45
MutPred		0.55		Gain of loop (P = 0.069);Gain of loop (P = 0.069);
MVP		0.62
MPC		0.87
ClinPred		0.91	D
GERP RS		2.1
Varity_R		0.30
gMVP		0.42

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: rs1371116420; hg19: chr16-66613718;