rs112620134

Positions:

chr19-6368677-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_006012.4(CLPP):c.801G>A(p.Ala267=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 1,566,892 control chromosomes in the GnomAD database, including 100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0096 ( 13 hom., cov: 32)

Exomes 𝑓: 0.011 ( 87 hom. )

Consequence

CLPP
NM_006012.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -2.98

Variant links:

Genes affected

CLPP (HGNC:2084): (caseinolytic mitochondrial matrix peptidase proteolytic subunit) The protein encoded by this gene belongs to the peptidase family S14 and hydrolyzes proteins into small peptides in the presence of ATP and magnesium. The protein is transported into mitochondrial matrix and is associated with the inner mitochondrial membrane. [provided by RefSeq, Jul 2008]

CLPP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 19-6368677-G-A is Benign according to our data. Variant chr19-6368677-G-A is described in ClinVar as [Benign]. Clinvar id is 226523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.98 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00961 (1463/152234) while in subpopulation NFE AF= 0.0132 (895/68006). AF 95% confidence interval is 0.0124. There are 13 homozygotes in gnomad4. There are 725 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLPP	NM_006012.4 linkuse as main transcript	c.801G>A	p.Ala267=	synonymous_variant	6/6	ENST00000245816.11	NP_006003.1
CLPP	XM_047439486.1 linkuse as main transcript	c.897G>A	p.Ala299=	synonymous_variant	5/5		XP_047295442.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLPP	ENST00000245816.11 linkuse as main transcript	c.801G>A	p.Ala267=	synonymous_variant	6/6	1	NM_006012.4	ENSP00000245816	P1

Frequencies

GnomAD3 genomes

AF:

0.00962

AC:

1464

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0106

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00405

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0132

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00813

AC:

1395

AN:

171522

Hom.:

AF XY:

0.00797

AC XY:

729

AN XY:

91478

show subpopulations

Gnomad AFR exome

AF:

0.00604

Gnomad AMR exome

AF:

0.00473

Gnomad ASJ exome

AF:

0.0118

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00173

Gnomad FIN exome

AF:

0.00564

Gnomad NFE exome

AF:

0.0134

Gnomad OTH exome

AF:

0.00935

GnomAD4 exome

AF:

0.0112

AC:

15796

AN:

1414658

Hom.:

Cov.:

AF XY:

0.0110

AC XY:

7683

AN XY:

699678

show subpopulations

Gnomad4 AFR exome

AF:

0.00724

Gnomad4 AMR exome

AF:

0.00511

Gnomad4 ASJ exome

AF:

0.0136

Gnomad4 EAS exome

AF:

0.0000273

Gnomad4 SAS exome

AF:

0.00239

Gnomad4 FIN exome

AF:

0.00588

Gnomad4 NFE exome

AF:

0.0127

Gnomad4 OTH exome

AF:

0.0112

GnomAD4 genome

AF:

0.00961

AC:

1463

AN:

152234

Hom.:

Cov.:

AF XY:

0.00974

AC XY:

725

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00700

Gnomad4 AMR

AF:

0.0106

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00405

Gnomad4 NFE

AF:

0.0132

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.0120

Hom.:

Bravo

AF:

0.00961

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:6

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 18, 2018	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	CLPP: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 12, 2019	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Jul 13, 2017	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Nov 24, 2014

Ala267Ala in exon 6 of CLPP: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. It has been identified in 1.1% (92/8592) of Eur opean American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs112620134). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.11

DANN

Benign

0.43

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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