3-32482285-T-C

Position:

• chr3-32482285-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000205636.4(CMTM6):​c.*1675A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 151,728 control chromosomes in the GnomAD database, including 15,252 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 0.43 (15252 hom., cov: 30)
  • Exomes 𝑓: 0.30 (0 hom.)
• Consequence: CMTM6 ENST00000205636.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105

Genes affected

CMTM6 (HGNC:19177): (CKLF like MARVEL transmembrane domain containing 6) This gene belongs to the chemokine-like factor gene superfamily, a novel family that is similar to the chemokine and transmembrane 4 superfamilies. This gene is one of several chemokine-like factor genes located in a cluster on chromosome 3. This gene is widely expressed in many tissues, but the exact function of the encoded protein is unknown. [provided by RefSeq, Jul 2008]

CMTM7 (HGNC:19178): (CKLF like MARVEL transmembrane domain containing 7) This gene belongs to the chemokine-like factor gene superfamily, a novel family that is similar to the chemokine and transmembrane 4 superfamilies. This gene is one of several chemokine-like factor genes located in a cluster on chromosome 3. This gene acts as a tumor suppressor that regulates G1/S transition in the cell cycle, and epidermal growth factor receptor/protein kinase B signaling during tumor pathogenesis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMTM6	NM_017801.3	c.*1675A>G		3_prime_UTR_variant	4/4	ENST00000205636.4	NP_060271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMTM6	ENST00000205636.4	c.*1675A>G		3_prime_UTR_variant	4/4	1	NM_017801.3	ENSP00000205636	P1
CMTM7	ENST00000487007.1	c.*289-459T>C		intron_variant, NMD_transcript_variant		5		ENSP00000445027

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65284 AN: 151600 Hom.: 15207 Cov.: 30

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.419

GnomAD4 exome AF: 0.300 AC: 3 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.431 AC: 65378 AN: 151718 Hom.: 15252 Cov.: 30 AF XY: 0.424 AC XY: 31423 AN XY: 74122

Gnomad4 AFR AF: 0.614

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.509

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.417

Alfa AF: 0.376 Hom.: 14650

Bravo AF: 0.451

Asia WGS AF: 0.385 AC: 1338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.30
DANN	Benign	0.54

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: rs4796; hg19: chr3-32523777;