Variant 15-65154950-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_006660.5(CLPX):c.1443T>C(p.His481His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 1,614,162 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 12 hom. )

Consequence

CLPX
NM_006660.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.835

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 Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 15-65154950-A-G is Benign according to our data. Variant chr15-65154950-A-G is described in ClinVar as [Benign]. Clinvar id is 1639395.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-65154950-A-G is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.835 with no splicing effect.

BS2

High AC in GnomAd4 at 278 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLPX	NM_006660.5 linkuse as main transcript	c.1443T>C	p.His481His	synonymous_variant	11/14	ENST00000300107.7	NP_006651.2	O76031A0A024R5X7
CLPX	XM_011521164.4 linkuse as main transcript	c.1401T>C	p.His467His	synonymous_variant	10/13		XP_011519466.1
CLPX	NR_133680.2 linkuse as main transcript	n.1586T>C		non_coding_transcript_exon_variant	11/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CLPX	ENST00000300107.7 linkuse as main transcript	c.1443T>C	p.His481His	synonymous_variant	11/14	1	NM_006660.5	ENSP00000300107.3	O76031
CLPX	ENST00000559152.5 linkuse as main transcript	n.*590T>C		non_coding_transcript_exon_variant	11/14	1		ENSP00000453461.1	H0YM48
CLPX	ENST00000559152.5 linkuse as main transcript	n.*590T>C		3_prime_UTR_variant	11/14	1		ENSP00000453461.1	H0YM48
CLPX	ENST00000560166.1 linkuse as main transcript	n.292T>C		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.00184

AC:

280

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00253

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.00518

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00123

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00209

AC:

526

AN:

251446

Hom.:

AF XY:

0.00222

AC XY:

302

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.00283

Gnomad AMR exome

AF:

0.00176

Gnomad ASJ exome

AF:

0.00308

Gnomad EAS exome

AF:

0.00283

Gnomad SAS exome

AF:

0.00529

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00137

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00164

AC:

2399

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00179

AC XY:

1300

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00224

Gnomad4 AMR exome

AF:

0.00170

Gnomad4 ASJ exome

AF:

0.00264

Gnomad4 EAS exome

AF:

0.000856

Gnomad4 SAS exome

AF:

0.00544

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.00136

Gnomad4 OTH exome

AF:

0.00210

GnomAD4 genome

AF:

0.00183

AC:

278

AN:

152278

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

142

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00253

Gnomad4 AMR

AF:

0.00275

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00232

Gnomad4 SAS

AF:

0.00477

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00123

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00149

Hom.:

Bravo

AF:

0.00192

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 13, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

5.2

DANN

Benign

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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