16-66579843-A-G

Variant names:

• chr16-66579843-A-G
• NM_144673.3:c.236A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_144673.3(CMTM2):​c.236A>G​(p.Asn79Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CMTM2 NM_144673.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.78

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMTM2	NM_144673.3	c.236A>G	p.Asn79Ser	missense_variant	Exon 1 of 4	ENST00000268595.3	NP_653274.1
CMTM2	NM_001199317.2	c.236A>G	p.Asn79Ser	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.236A>G	p.Asn79Ser	missense_variant	Exon 1 of 4	1	NM_144673.3	ENSP00000268595.2
CMTM2	ENST00000379486.6	c.236A>G	p.Asn79Ser	missense_variant	Exon 1 of 3	1		ENSP00000368800.2
CMTM2	ENST00000569316.1	n.91+145A>G		intron_variant	Intron 1 of 3	5		ENSP00000454319.1
ENSG00000260650	ENST00000568430.1	n.*140T>C		downstream_gene_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.236A>G (p.N79S) alteration is located in exon 1 (coding exon 1) of the CMTM2 gene. This alteration results from a A to G substitution at nucleotide position 236, causing the asparagine (N) at amino acid position 79 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.096	.;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	1.0	L;L
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.9	D;D
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.66
MutPred		0.67		Loss of ubiquitination at K76 (P = 0.045);Loss of ubiquitination at K76 (P = 0.045);
MVP		0.81
MPC		0.66
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.22
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-66613746;