Variant 16-66622206-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_181521.3(CMTM4):c.479C>T(p.Ala160Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,461,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

CMTM4
NM_181521.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.61

Variant links:

Genes affected

CMTM4 (HGNC:19175): (CKLF like MARVEL transmembrane domain containing 4) This gene belongs to the chemokine-like factor gene superfamily, a novel family that is similar to the chemokine and the transmembrane 4 superfamilies of signaling molecules. This gene is one of several chemokine-like factor genes located in a cluster on chromosome 16. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

CMTM4 links:

CMTM4 (HGNC:):

CMTM4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.321818).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMTM4	NM_181521.3 linkuse as main transcript	c.479C>T	p.Ala160Val	missense_variant	4/4	ENST00000394106.7	NP_852662.1	Q8IZR5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CMTM4	ENST00000394106.7 linkuse as main transcript	c.479C>T	p.Ala160Val	missense_variant	4/4	1	NM_181521.3	ENSP00000377666.2	Q8IZR5-2
CMTM4	ENST00000330687.8 linkuse as main transcript	c.479C>T	p.Ala160Val	missense_variant	4/5	1		ENSP00000333833.4	Q8IZR5-1
CMTM4	ENST00000563952.1 linkuse as main transcript	c.392C>T	p.Ala131Val	missense_variant	4/4	1		ENSP00000456380.1	Q8IZR5-3
CMTM4	ENST00000561680.5 linkuse as main transcript	c.197C>T	p.Ala66Val	missense_variant	3/5	2		ENSP00000464316.1	J3QRP2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1461414

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

726944

show subpopulations

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:

0.0000188

Gnomad4 NFE exome

AF:

0.0000243

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000122

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 14, 2022

The c.479C>T (p.A160V) alteration is located in exon 4 (coding exon 4) of the CMTM4 gene. This alteration results from a C to T substitution at nucleotide position 479, causing the alanine (A) at amino acid position 160 to be replaced by a valine (V). 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

0.40

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.072

T;T;.;.

Eigen

Benign

-0.015

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.88

D;D;D;D

M_CAP

Benign

0.0076

MetaRNN

Benign

0.32

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.76

N;.;N;.

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-2.7

D;.;D;D

REVEL

Benign

0.16

Sift

Benign

0.095

T;.;T;T

Sift4G

Benign

0.17

T;T;T;T

Polyphen

0.16

B;.;.;.

Vest4

0.44

MutPred

0.71

Gain of MoRF binding (P = 0.2761);.;Gain of MoRF binding (P = 0.2761);.;

MVP

0.25

MPC

0.67

ClinPred

0.51

GERP RS

6.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.61

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over