rs723840

Positions:

• chr14-23379102-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

CMTM5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMTM5	NM_001288746.2	c.552C>T	p.Asp184Asp	synonymous_variant	4/6	ENST00000339180.9	NP_001275675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMTM5	ENST00000339180.9	c.552C>T	p.Asp184Asp	synonymous_variant	4/6	1	NM_001288746.2	ENSP00000344819.4

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

GnomAD3 exomes AF: 0.444 AC: 111368 AN: 250924 Hom.: 26910 AF XY: 0.447 AC XY: 60564 AN XY: 135590

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 SAS exome AF: 0.477

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

Gnomad4 AFR exome AF: 0.793

Gnomad4 AMR exome AF: 0.287

Gnomad4 ASJ exome AF: 0.533

Gnomad4 EAS exome AF: 0.272

Gnomad4 SAS exome AF: 0.477

Gnomad4 FIN exome AF: 0.433

Gnomad4 NFE exome AF: 0.463

Gnomad4 OTH exome AF: 0.469

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

Gnomad4 AFR AF: 0.786

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.545

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.538

Alfa AF: 0.484 Hom.: 24737

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	6.8
DANN	Benign	0.81

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

LitVar

Other links and lift over

dbSNP: rs723840; hg19: chr14-23848311; COSMIC: COSV59305185; COSMIC: COSV59305185;