Variant X-155063978-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001018024.3(CMC4):c.46A>C(p.Lys16Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000037 in 1,079,695 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0000037 ( 0 hom. 3 hem. )

Consequence

CMC4
NM_001018024.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.18

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.29571843).

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMC4	NM_001018024.3 linkuse as main transcript	c.46A>C	p.Lys16Gln	missense_variant	2/3	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.46A>C	p.Lys16Gln	missense_variant	2/3	1	NM_001018024.3	ENSP00000358496.3	P56277-1
ENSG00000288258	ENST00000504061.1 linkuse as main transcript	n.*60A>C		non_coding_transcript_exon_variant	2/3	3		ENSP00000427132.1	A0A0G2JKI4
ENSG00000288258	ENST00000504061.1 linkuse as main transcript	n.*60A>C		3_prime_UTR_variant	2/3	3		ENSP00000427132.1	A0A0G2JKI4
CMC4	ENST00000369479.1 linkuse as main transcript	c.46A>C	p.Lys16Gln	missense_variant	2/3	3		ENSP00000358491.1	P56277-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000123

AC:

AN:

163204

Hom.:

AF XY:

0.0000374

AC XY:

AN XY:

53416

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000262

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000370

AC:

AN:

1079695

Hom.:

Cov.:

AF XY:

0.00000854

AC XY:

AN XY:

351229

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:

0.00

Gnomad4 NFE exome

AF:

0.00000478

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

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

Nov 04, 2021

The c.46A>C (p.K16Q) alteration is located in exon 2 (coding exon 1) of the CMC4 gene. This alteration results from a A to C substitution at nucleotide position 46, causing the lysine (K) at amino acid position 16 to be replaced by a glutamine (Q). 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

Benign

0.16

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.048

T;T

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.80

.;T

M_CAP

Benign

0.0091

MetaRNN

Benign

0.30

T;T

MetaSVM

Benign

-0.84

MutationTaster

Benign

0.55

N;N

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.12

Sift

Benign

0.17

T;T

Sift4G

Uncertain

0.038

D;D

Polyphen

0.85

P;P

Vest4

0.36

MutPred

0.42

Loss of methylation at K16 (P = 5e-04);Loss of methylation at K16 (P = 5e-04);

MVP

0.28

MPC

1.2

ClinPred

0.96

GERP RS

4.1

Varity_R

0.26

gMVP

0.37

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