Variant X-155061901-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -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

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -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 id is 1205949.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-155061901-C-G is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMC4	NM_001018024.3 linkuse as main transcript	c.149G>C	p.Cys50Ser	missense_variant	3/3	ENST00000369484.8	NP_001018024.1	P56277-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CMC4	ENST00000369484.8 linkuse as main transcript	c.149G>C	p.Cys50Ser	missense_variant	3/3	1	NM_001018024.3	ENSP00000358496.3	P56277-1
ENSG00000288258	ENST00000504061.1 linkuse as main transcript	n.*163G>C		non_coding_transcript_exon_variant	3/3	3		ENSP00000427132.1	A0A0G2JKI4
ENSG00000288258	ENST00000504061.1 linkuse as main transcript	n.*163G>C		3_prime_UTR_variant	3/3	3		ENSP00000427132.1	A0A0G2JKI4
CMC4	ENST00000369479.1 linkuse as main transcript	c.149G>C	p.Cys50Ser	missense_variant	3/3	3		ENSP00000358491.1	P56277-1

Frequencies

GnomAD3 genomes

AF:

0.000321

AC:

AN:

112239

Hom.:

Cov.:

AF XY:

0.000320

AC XY:

AN XY:

34403

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

GnomAD3 exomes

AF:

0.000379

AC:

AN:

182134

Hom.:

AF XY:

0.000480

AC XY:

AN XY:

66682

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 SAS 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

Gnomad4 AFR exome

AF:

0.0000379

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:

0.000885

Gnomad4 OTH exome

AF:

0.000304

GnomAD4 genome

AF:

0.000321

AC:

AN:

112294

Hom.:

Cov.:

AF XY:

0.000319

AC XY:

AN XY:

34468

show subpopulations

Gnomad4 AFR

AF:

0.0000323

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000164

Gnomad4 NFE

AF:

0.000639

Gnomad4 OTH

AF:

0.00

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

Significance: Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Pathogenic

0.44

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

T;T

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.75

.;T

M_CAP

Pathogenic

0.34

MetaRNN

Uncertain

0.64

D;D

MetaSVM

Uncertain

-0.064

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-7.3

D;D

REVEL

Pathogenic

0.84

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.74

MutPred

0.80

Gain of phosphorylation at C50 (P = 0.0292);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

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

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