CMTM2 p.Ile140Met

Variant names:

• chr16-66580160-A-G
• NM_144673.3:c.420A>G
• CMTM2 p.Ile140Met

Variant summary

Our verdict is

Likely benign

-2 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_144673.3(CMTM2):​c.420A>G​(p.Ile140Met) 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CMTM2 NM_144673.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0670
• 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]

ENSG00000260650 (HGNC:58533):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.049).
• BP6: Variant 16-66580160-A-G is Benign according to our data. Variant chr16-66580160-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2493903.Status of the report is criteria_provided_single_submitter, 1 stars.

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.420A>G	p.Ile140Met	missense	Exon 2 of 4	NP_653274.1	Q8TAZ6-1
	CMTM2	NM_001199317.2		c.285+268A>G		intron	N/A	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.420A>G	p.Ile140Met	missense	Exon 2 of 4	ENSP00000268595.2	Q8TAZ6-1
	CMTM2	ENST00000379486.6	TSL:1	c.285+268A>G		intron	N/A	ENSP00000368800.2	Q8TAZ6-2
	ENSG00000260650	ENST00000568430.1	TSL:4	n.378T>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.13
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	11
DANN	Benign	0.94
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.00089	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.067
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.37	N
REVEL	Benign	0.049
Sift	Benign	0.49	T
Sift4G	Benign	0.81	T
Varity_R		0.090
gMVP		0.17

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-66614063;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline