chr14-23379102-C-T

Variant names:

• chr14-23379102-C-T
• rs723840
• NM_001288746.2:c.552C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001288746.2(CMTM5):​c.552C>T​(p.Asp184Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 1,613,394 control chromosomes in the GnomAD database, including 183,776 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.54 (23899 hom., cov: 31)
  • Exomes 𝑓: 0.46 (159877 hom.)
• Consequence: CMTM5 NM_001288746.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.882
• Publications: 22 publications found

Genes affected

CMTM5 (HGNC:19176): (CKLF like MARVEL transmembrane domain containing 5) This gene encodes a member of the chemokine-like factor superfamily. This family of genes encodes multi-pass membrane proteins that are similar to both the chemokine and the transmembrane 4 superfamilies of signaling molecules. The encoded protein may exhibit tumor suppressor activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP7: Synonymous conserved (PhyloP=-0.882 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288746.2. 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
	CMTM5	NM_001288746.2	MANE Select	c.552C>T	p.Asp184Asp	synonymous	Exon 4 of 6	NP_001275675.1
	CMTM5	NM_138460.3		c.351C>T	p.Asp117Asp	synonymous	Exon 3 of 5	NP_612469.1
	CMTM5	NM_001288744.2		c.198C>T	p.Asp66Asp	synonymous	Exon 2 of 4	NP_001275673.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CMTM5	ENST00000339180.9	TSL:1 MANE Select	c.552C>T	p.Asp184Asp	synonymous	Exon 4 of 6	ENSP00000344819.4
	CMTM5	ENST00000359320.7	TSL:1	c.351C>T	p.Asp117Asp	synonymous	Exon 3 of 5	ENSP00000352270.3
	CMTM5	ENST00000555731.5	TSL:1	c.237C>T	p.Asp79Asp	synonymous	Exon 3 of 5	ENSP00000451514.1

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81601 AN: 151850 Hom.: 23856 Cov.: 31

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.533

GnomAD2 exomes AF: 0.444 AC: 111368 AN: 250924 AF XY: 0.447

Gnomad AFR exome AF: 0.792

Gnomad AMR exome AF: 0.271

Gnomad ASJ exome AF: 0.534

Gnomad EAS exome AF: 0.254

Gnomad FIN exome AF: 0.440

Gnomad NFE exome AF: 0.460

Gnomad OTH exome AF: 0.465

GnomAD4 exome AF: 0.461 AC: 673945 AN: 1461426 Hom.: 159877 Cov.: 47 AF XY: 0.461 AC XY: 335295 AN XY: 727062

African (AFR) AF: 0.793 AC: 26559 AN: 33472

American (AMR) AF: 0.287 AC: 12825 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 13929 AN: 26112

East Asian (EAS) AF: 0.272 AC: 10814 AN: 39698

South Asian (SAS) AF: 0.477 AC: 41101 AN: 86240

European-Finnish (FIN) AF: 0.433 AC: 23117 AN: 53374

Middle Eastern (MID) AF: 0.512 AC: 2951 AN: 5768

European-Non Finnish (NFE) AF: 0.463 AC: 514355 AN: 1111684

Other (OTH) AF: 0.469 AC: 28294 AN: 60382

GnomAD4 genome AF: 0.538 AC: 81699 AN: 151968 Hom.: 23899 Cov.: 31 AF XY: 0.533 AC XY: 39601 AN XY: 74270

African (AFR) AF: 0.786 AC: 32582 AN: 41436

American (AMR) AF: 0.406 AC: 6207 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1893 AN: 3472

East Asian (EAS) AF: 0.263 AC: 1354 AN: 5150

South Asian (SAS) AF: 0.470 AC: 2260 AN: 4812

European-Finnish (FIN) AF: 0.446 AC: 4714 AN: 10566

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31029 AN: 67936

Other (OTH) AF: 0.538 AC: 1136 AN: 2112

Alfa AF: 0.503 Hom.: 44379

Bravo AF: 0.542

Asia WGS AF: 0.419 AC: 1454 AN: 3478

EpiCase AF: 0.468

EpiControl AF: 0.478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	6.8
DANN	Benign	0.81
PhyloP100		-0.88
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: rs723840; hg19: chr14-23848311; COSMIC: COSV59305185; COSMIC: COSV59305185;