16-66580105-T-C

Variant names:

• chr16-66580105-T-C
• rs2290182
• NM_144673.3:c.365T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144673.3(CMTM2):​c.365T>C​(p.Ile122Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,614,022 control chromosomes in the GnomAD database, including 18,379 homozygotes. 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 0.17 (2720 hom., cov: 32)
  • Exomes 𝑓: 0.13 (15659 hom.)
• Consequence: CMTM2 NM_144673.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.02
• Publications: 38 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0058350563).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CMTM2	NM_144673.3	MANE Select	c.365T>C	p.Ile122Thr	missense	Exon 2 of 4	NP_653274.1
	CMTM2	NM_001199317.2		c.285+213T>C		intron	N/A	NP_001186246.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CMTM2	ENST00000268595.3	TSL:1 MANE Select	c.365T>C	p.Ile122Thr	missense	Exon 2 of 4	ENSP00000268595.2
	CMTM2	ENST00000379486.6	TSL:1	c.285+213T>C		intron	N/A	ENSP00000368800.2
	ENSG00000260650	ENST00000568430.1	TSL:4	n.433A>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26214 AN: 152068 Hom.: 2717 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.0956

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.156

GnomAD2 exomes AF: 0.180 AC: 45384 AN: 251484 AF XY: 0.174

Gnomad AFR exome AF: 0.261

Gnomad AMR exome AF: 0.323

Gnomad ASJ exome AF: 0.107

Gnomad EAS exome AF: 0.300

Gnomad FIN exome AF: 0.0995

Gnomad NFE exome AF: 0.116

Gnomad OTH exome AF: 0.164

GnomAD4 exome AF: 0.132 AC: 192696 AN: 1461836 Hom.: 15659 Cov.: 34 AF XY: 0.133 AC XY: 96931 AN XY: 727230

African (AFR) AF: 0.265 AC: 8864 AN: 33476

American (AMR) AF: 0.313 AC: 13987 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 2886 AN: 26136

East Asian (EAS) AF: 0.309 AC: 12269 AN: 39700

South Asian (SAS) AF: 0.221 AC: 19023 AN: 86258

European-Finnish (FIN) AF: 0.105 AC: 5590 AN: 53416

Middle Eastern (MID) AF: 0.142 AC: 817 AN: 5768

European-Non Finnish (NFE) AF: 0.108 AC: 120551 AN: 1111964

Other (OTH) AF: 0.144 AC: 8709 AN: 60394

GnomAD4 genome AF: 0.172 AC: 26246 AN: 152186 Hom.: 2720 Cov.: 32 AF XY: 0.173 AC XY: 12865 AN XY: 74434

African (AFR) AF: 0.263 AC: 10917 AN: 41518

American (AMR) AF: 0.215 AC: 3291 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 369 AN: 3470

East Asian (EAS) AF: 0.292 AC: 1509 AN: 5164

South Asian (SAS) AF: 0.218 AC: 1050 AN: 4816

European-Finnish (FIN) AF: 0.0956 AC: 1015 AN: 10616

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7574 AN: 67994

Other (OTH) AF: 0.157 AC: 331 AN: 2112

Alfa AF: 0.135 Hom.: 7233

Bravo AF: 0.190

TwinsUK AF: 0.107 AC: 396

ALSPAC AF: 0.117 AC: 449

ESP6500AA AF: 0.266 AC: 1173

ESP6500EA AF: 0.113 AC: 973

ExAC AF: 0.180 AC: 21834

Asia WGS AF: 0.265 AC: 920 AN: 3478

EpiCase AF: 0.114

EpiControl AF: 0.116

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.0058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		3.0
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.063
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.054	T
Polyphen		0.058	B
Vest4		0.070
MPC		0.34
ClinPred		0.026	T
GERP RS		3.4
Varity_R		0.14
gMVP		0.41
Mutation Taster		=100/0	polymorphism (auto)

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: rs2290182; hg19: chr16-66614008; COSMIC: COSV51749466; COSMIC: COSV51749466;