Variant 16-66622114-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_181521.3(CMTM4):c.571C>T(p.Arg191Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000885 in 1,604,278 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: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000091 ( 0 hom. )

Consequence

CMTM4
NM_181521.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.15

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21860233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMTM4	NM_181521.3 link	c.571C>T	p.Arg191Cys	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 link	c.571C>T	p.Arg191Cys	missense_variant	4/4	1	NM_181521.3	ENSP00000377666.2	Q8IZR5-2
CMTM4	ENST00000330687.8 link	c.571C>T	p.Arg191Cys	missense_variant	4/5	1		ENSP00000333833.4	Q8IZR5-1
CMTM4	ENST00000563952.1 link	c.484C>T	p.Arg162Cys	missense_variant	4/4	1		ENSP00000456380.1	Q8IZR5-3
CMTM4	ENST00000561680.5 link	c.289C>T	p.Arg97Cys	missense_variant	3/5	2		ENSP00000464316.1	J3QRP2

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000161

AC:

AN:

235518

Hom.:

AF XY:

0.000205

AC XY:

AN XY:

126960

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000911

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000566

Gnomad SAS exome

AF:

0.000771

Gnomad FIN exome

AF:

0.0000489

Gnomad NFE exome

AF:

0.000104

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000909

AC:

132

AN:

1452064

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

721192

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000694

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000853

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000470

Gnomad4 OTH exome

AF:

0.0000499

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000772

Hom.:

Bravo

AF:

0.0000453

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000107

AC:

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

Oct 12, 2024

The c.571C>T (p.R191C) 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 571, causing the arginine (R) at amino acid position 191 to be replaced by a cysteine (C). 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

0.51

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.14

T;T;.;.

Eigen

Uncertain

0.65

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.95

D;D;D;D

M_CAP

Benign

0.020

MetaRNN

Benign

0.22

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;.;L;.

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-2.4

N;.;N;D

REVEL

Uncertain

0.35

Sift

Uncertain

0.0050

D;.;D;D

Sift4G

Uncertain

0.0050

D;D;D;D

Polyphen

1.0

D;.;.;.

Vest4

0.75

MVP

0.50

MPC

1.6

ClinPred

0.19

GERP RS

6.1

Varity_R

0.13

gMVP

0.56

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over