14-23379035-T-A

Position:

• chr14-23379035-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001288746.2(CMTM5):​c.485T>A​(p.Phe162Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CMTM5 NM_001288746.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.65

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.783

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMTM5	NM_001288746.2	c.485T>A	p.Phe162Tyr	missense_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.485T>A	p.Phe162Tyr	missense_variant	4/6	1	NM_001288746.2	ENSP00000344819.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461834 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727232

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Dec 27, 2023

The c.284T>A (p.F95Y) alteration is located in exon 3 (coding exon 3) of the CMTM5 gene. This alteration results from a T to A substitution at nucleotide position 284, causing the phenylalanine (F) at amino acid position 95 to be replaced by a tyrosine (Y). 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	Pathogenic	0.69
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	.;.;T;.;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.71	.;T;T;T;T
M_CAP	Pathogenic	0.47	D
MetaRNN	Pathogenic	0.78	D;D;D;D;D
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Uncertain	2.4	.;.;M;.;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-2.4	.;N;N;N;N
REVEL	Uncertain	0.31
Sift	Uncertain	0.010	.;D;D;D;D
Sift4G	Pathogenic	0.0	.;D;D;D;D
Polyphen		1.0	D;D;D;D;D
Vest4		0.61, 0.38, 0.46, 0.48
MutPred		0.51		.;.;Loss of glycosylation at S159 (P = 0.1582);.;.;
MVP		0.65
MPC		0.68
ClinPred		0.97	D
GERP RS		5.8
Varity_R		0.47
gMVP		0.62

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: chr14-23848244;