3-32502729-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017801.3(CMTM6):c.17T>G(p.Val6Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CMTM6 NM_017801.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.27

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CMTM6	NM_017801.3	c.17T>G	p.Val6Gly	missense_variant	1/4	ENST00000205636.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CMTM6	ENST00000205636.4	c.17T>G	p.Val6Gly	missense_variant	1/4	1	NM_017801.3	P1
CMTM6	ENST00000495177.1	n.68T>G		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2021

The c.17T>G (p.V6G) alteration is located in exon 1 (coding exon 1) of the CMTM6 gene. This alteration results from a T to G substitution at nucleotide position 17, causing the valine (V) at amino acid position 6 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
Cadd	Pathogenic	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.56	T
M_CAP	Pathogenic	0.82	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.061	T
Polyphen		0.99	D
Vest4		0.44
MutPred		0.22		Gain of glycosylation at Y7 (P = 1e-04);
MVP		0.22
MPC		0.71
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.51
gMVP		0.69

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-32544221;