Genetic Variant CMTM6:c.*1675A>G (chr3-32482285-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017801.3(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
NM_017801.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.105

Publications

20 publications found

Variant links:

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]

CMTM6 links:

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]

CMTM7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CMTM6	NM_017801.3 link	c.*1675A>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000205636.4	NP_060271.1	Q9NX76

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CMTM6	ENST00000205636.4 link	c.*1675A>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_017801.3	ENSP00000205636.3		Q9NX76
CMTM7	ENST00000487007.1 link	n.*289-459T>C		intron_variant	Intron 3 of 3	5		ENSP00000445027.1		H0YGW1

Frequencies

GnomAD3 genomes

AF:

0.431

AC:

65284

AN:

151600

Hom.:

15207

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.167

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.333

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.592

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.431

AC:

65378

AN:

151718

Hom.:

15252

Cov.:

AF XY:

0.424

AC XY:

31423

AN XY:

74122

show subpopulations

African (AFR)

AF:

0.614

AC:

25393

AN:

41324

American (AMR)

AF:

0.383

AC:

5848

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.394

AC:

1365

AN:

3464

East Asian (EAS)

AF:

0.509

AC:

2619

AN:

5148

South Asian (SAS)

AF:

0.318

AC:

1529

AN:

4804

European-Finnish (FIN)

AF:

0.273

AC:

2881

AN:

10542

Middle Eastern (MID)

AF:

0.397

AC:

116

AN:

292

European-Non Finnish (NFE)

AF:

0.362

AC:

24577

AN:

67874

Other (OTH)

AF:

0.417

AC:

878

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1759

3519

5278

7038

8797

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

592

1184

1776

2368

2960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.383

Hom.:

19425

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

(source)

DANN

Benign

0.54

PhyloP100

0.10

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over