rs931772089

Variant names:

• chr16-66588094-C-T
• rs931772089
• NM_144673.3:c.722C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144673.3(CMTM2):​c.722C>T​(p.Pro241Leu) 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 benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CMTM2 NM_144673.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.99
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13089317).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144673.3. 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
	CMTM2	NM_144673.3	MANE Select	c.722C>T	p.Pro241Leu	missense	Exon 4 of 4	NP_653274.1	Q8TAZ6-1
	CMTM2	NM_001199317.2		c.563C>T	p.Pro188Leu	missense	Exon 3 of 3	NP_001186246.1	Q8TAZ6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CMTM2	ENST00000268595.3	TSL:1 MANE Select	c.722C>T	p.Pro241Leu	missense	Exon 4 of 4	ENSP00000268595.2	Q8TAZ6-1
	CMTM2	ENST00000379486.6	TSL:1	c.563C>T	p.Pro188Leu	missense	Exon 3 of 3	ENSP00000368800.2	Q8TAZ6-2
	CMTM2	ENST00000532362.1	TSL:2	n.366C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	3.5
DANN	Benign	0.43
DEOGEN2	Benign	0.0056	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		-2.0
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.076
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.042	D
Polyphen		0.78	P
Vest4		0.22
MutPred		0.21		Gain of MoRF binding (P = 0.0199)
MVP		0.51
MPC		0.21
ClinPred		0.20	T
GERP RS		-4.6
Varity_R		0.039
gMVP		0.14

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

Other links and lift over

dbSNP: rs931772089; hg19: chr16-66621997;