Variant 15-65150884-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006660.5(CLPX):c.1841A>G(p.Glu614Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000293 in 1,611,788 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 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00031 ( 0 hom. )

Consequence

CLPX
NM_006660.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.00

Variant links:

Genes affected

CLPX (HGNC:2088): (caseinolytic mitochondrial matrix peptidase chaperone subunit X) The protein encoded by this gene is part of a protease found in mitochondria. This protease is ATP-dependent and targets specific proteins for degradation. The protease consists of two heptameric rings of the CLPP catalytic subunit sandwiched between two hexameric rings of the chaperone subunit encoded by this gene. Targeted proteins are unwound by this protein and then passed on to the CLPP subunit for degradation. Two transcript variants, one protein-coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Nov 2015]

CLPX links:

CLPX (HGNC:):

CLPX links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1537593).

BS2

High AC in GnomAd4 at 26 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLPX	NM_006660.5 linkuse as main transcript	c.1841A>G	p.Glu614Gly	missense_variant	14/14	ENST00000300107.7	NP_006651.2	O76031A0A024R5X7
CLPX	XM_011521164.4 linkuse as main transcript	c.1799A>G	p.Glu600Gly	missense_variant	13/13		XP_011519466.1
CLPX	NR_133680.2 linkuse as main transcript	n.1984A>G		non_coding_transcript_exon_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CLPX	ENST00000300107.7 linkuse as main transcript	c.1841A>G	p.Glu614Gly	missense_variant	14/14	1	NM_006660.5	ENSP00000300107.3	O76031
CLPX	ENST00000559152.5 linkuse as main transcript	n.*988A>G		non_coding_transcript_exon_variant	14/14	1		ENSP00000453461.1	H0YM48
CLPX	ENST00000559152.5 linkuse as main transcript	n.*988A>G		3_prime_UTR_variant	14/14	1		ENSP00000453461.1	H0YM48

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000152

AC:

AN:

249334

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

134812

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:

0.0000463

Gnomad NFE exome

AF:

0.000318

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000306

AC:

447

AN:

1459618

Hom.:

Cov.:

AF XY:

0.000280

AC XY:

203

AN XY:

726180

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:

0.0000938

Gnomad4 NFE exome

AF:

0.000381

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000171

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000229

Hom.:

Bravo

AF:

0.000174

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000222

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

Feb 06, 2023

The c.1841A>G (p.E614G) alteration is located in exon 14 (coding exon 14) of the CLPX gene. This alteration results from a A to G substitution at nucleotide position 1841, causing the glutamic acid (E) at amino acid position 614 to be replaced by a glycine (G). 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

0.24

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.013

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.3

REVEL

Benign

0.087

Sift

Benign

0.045

Sift4G

Benign

0.19

Polyphen

0.15

Vest4

0.35

MVP

0.13

MPC

0.48

ClinPred

0.18

GERP RS

5.9

Varity_R

0.12

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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