Genetic Variant CMC4:p.Cys50Ser (chrX-155061901-C-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6BS2

The NM_001018024.3(CMC4):c.149G>C(p.Cys50Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000658 in 1,210,114 control chromosomes in the GnomAD database, including 1 homozygotes. There are 237 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., 11 hem., cov: 23)

Exomes 𝑓: 0.00069 ( 1 hom. 226 hem. )

Consequence

CMC4
NM_001018024.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:2

Conservation

PhyloP100: 5.51

Publications

3 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: Likely_benign. The variant received -5 ACMG points.

BP6

Variant X-155061901-C-G is Benign according to our data. Variant chrX-155061901-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1205949.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Hemizygotes in GnomAd4 at 11 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.149G>C	p.Cys50Ser	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.149G>C	p.Cys50Ser	missense	Exon 3 of 3	ENSP00000358496.3	P56277-1
ENSG00000288258	ENST00000504061.1	TSL:3	n.*163G>C		non_coding_transcript_exon	Exon 3 of 3	ENSP00000427132.1	A0A0G2JKI4
ENSG00000288258	ENST00000504061.1	TSL:3	n.*163G>C		3_prime_UTR	Exon 3 of 3	ENSP00000427132.1	A0A0G2JKI4

Frequencies

GnomAD3 genomes

AF:

0.000321

AC:

AN:

112239

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000324

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:

0.000164

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000639

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000379

AC:

AN:

182134

AF XY:

0.000480

show subpopulations

Gnomad AFR exome

AF:

0.0000762

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000835

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000692

AC:

760

AN:

1097820

Hom.:

Cov.:

AF XY:

0.000622

AC XY:

226

AN XY:

363190

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26391

American (AMR)

AF:

0.00

AC:

AN:

35158

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19373

East Asian (EAS)

AF:

0.00

AC:

AN:

30179

South Asian (SAS)

AF:

0.00

AC:

AN:

54066

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40524

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.000885

AC:

745

AN:

841919

Other (OTH)

AF:

0.000304

AC:

AN:

46074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

116

145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<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:

0.000321

AC:

AN:

112294

Hom.:

Cov.:

AF XY:

0.000319

AC XY:

AN XY:

34468

show subpopulations

African (AFR)

AF:

0.0000323

AC:

AN:

30933

American (AMR)

AF:

0.00

AC:

AN:

10621

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2647

East Asian (EAS)

AF:

0.00

AC:

AN:

3593

South Asian (SAS)

AF:

0.00

AC:

AN:

2729

European-Finnish (FIN)

AF:

0.000164

AC:

AN:

6087

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.000639

AC:

AN:

53236

Other (OTH)

AF:

0.00

AC:

AN:

1544

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000347

Hom.:

Bravo

AF:

0.000264

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00138

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.000892

AC:

ExAC

AF:

0.000461

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Pathogenic

0.44

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.75

M_CAP

Pathogenic

0.34

MetaRNN

Uncertain

0.64

MetaSVM

Uncertain

-0.064

PhyloP100

5.5

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-7.3

REVEL

Pathogenic

0.84

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.74

MutPred

0.80

Gain of phosphorylation at C50 (P = 0.0292)

MVP

0.22

MPC

1.4

ClinPred

0.58

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.94

gMVP

0.78

Mutation Taster

=74/26

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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