Genetic Variant CMC4:p.Arg63Gln (chrX-155061862-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001018024.3(CMC4):c.188G>A(p.Arg63Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,206,725 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000013 ( 0 hom. 8 hem. )

Consequence

CMC4
NM_001018024.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.656

Publications

0 publications found

Variant links:

Genes affected

CMC4 (HGNC:35428): (C-X9-C motif containing 4) This gene was identified by involvement in some t(X;14) translocations associated with mature T-cell proliferations. This region has a complex gene structure, with a common promoter and 5' exon spliced to two different sets of 3' exons that encode two different proteins. This gene represents the downstream 8 kDa protein that localizes to mitochondria.[provided by RefSeq, Mar 2009]

CMC4 links:

ENSG00000288258 (HGNC:):

ENSG00000288258 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04144472).

BS2

High Hemizygotes in GnomAdExome4 at 8 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001018024.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CMC4	NM_001018024.3	MANE Select	c.188G>A	p.Arg63Gln	missense	Exon 3 of 3	NP_001018024.1	P56277-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CMC4	ENST00000369484.8	TSL:1 MANE Select	c.188G>A	p.Arg63Gln	missense	Exon 3 of 3	ENSP00000358496.3	P56277-1
ENSG00000288258	ENST00000504061.1	TSL:3	n.*202G>A		non_coding_transcript_exon	Exon 3 of 3	ENSP00000427132.1	A0A0G2JKI4
ENSG00000288258	ENST00000504061.1	TSL:3	n.*202G>A		3_prime_UTR	Exon 3 of 3	ENSP00000427132.1	A0A0G2JKI4

Frequencies

GnomAD3 genomes

AF:

0.00000891

AC:

AN:

112227

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000113

AC:

AN:

176984

AF XY:

0.0000323

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000756

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000128

AC:

AN:

1094498

Hom.:

Cov.:

AF XY:

0.0000222

AC XY:

AN XY:

360154

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26275

American (AMR)

AF:

0.00

AC:

AN:

34812

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19293

East Asian (EAS)

AF:

0.000100

AC:

AN:

29982

South Asian (SAS)

AF:

0.0000375

AC:

AN:

53308

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40437

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4131

European-Non Finnish (NFE)

AF:

0.00000952

AC:

AN:

840306

Other (OTH)

AF:

0.0000218

AC:

AN:

45954

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000891

AC:

AN:

112227

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

34399

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30833

American (AMR)

AF:

0.00

AC:

AN:

10625

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2644

East Asian (EAS)

AF:

0.00

AC:

AN:

3590

South Asian (SAS)

AF:

0.00

AC:

AN:

2753

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6072

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53260

Other (OTH)

AF:

0.00

AC:

AN:

1524

Age Distribution

Genome Hom

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.0

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.22

M_CAP

Benign

0.012

MetaRNN

Benign

0.041

MetaSVM

Benign

-0.99

PhyloP100

-0.66

PrimateAI

Benign

0.25

PROVEAN

Benign

0.22

REVEL

Benign

0.010

Sift

Benign

0.34

Sift4G

Benign

0.42

Polyphen

0.13

Vest4

0.028

MVP

0.067

MPC

0.50

ClinPred

0.064

GERP RS

1.5

Varity_R

0.046

gMVP

0.22

Mutation Taster

=95/5

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over