dbSNP rs769823589: CLPP:p.Thr51Thr (chr19-6361727-G-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_006012.4(CLPP):c.153G>A(p.Thr51Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000303 in 1,354,944 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 Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

CLPP
NM_006012.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0710

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Perrault syndrome 3
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P
Perrault syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CLPP links:

ENSG00000269802 (HGNC:):

ENSG00000269802 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 19-6361727-G-A is Benign according to our data. Variant chr19-6361727-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 505096.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.071 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLPP	NM_006012.4 link	c.153G>A	p.Thr51Thr	synonymous_variant	Exon 1 of 6	ENST00000245816.11	NP_006003.1	Q16740
CLPP	XM_047439486.1 link	c.153G>A	p.Thr51Thr	synonymous_variant	Exon 1 of 5		XP_047295442.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLPP	ENST00000245816.11 link	c.153G>A	p.Thr51Thr	synonymous_variant	Exon 1 of 6	1	NM_006012.4	ENSP00000245816.3		Q16740

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000450

AC:

AN:

111080

AF XY:

0.0000667

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000465

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000303

AC:

AN:

1354944

Hom.:

Cov.:

AF XY:

0.0000376

AC XY:

AN XY:

665262

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30856

American (AMR)

AF:

0.00

AC:

AN:

32534

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22740

East Asian (EAS)

AF:

0.00

AC:

AN:

35546

South Asian (SAS)

AF:

0.000201

AC:

AN:

74502

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33020

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5490

European-Non Finnish (NFE)

AF:

0.0000235

AC:

AN:

1063720

Other (OTH)

AF:

0.0000177

AC:

AN:

56536

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jun 02, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Thr51Thr in exon 1 of CLPP: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 1/1384 South Asian c hromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute .org; dbSNP rs769823589). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

8.6

(source)

DANN

Benign

0.91

PhyloP100

-0.071

PromoterAI

-0.041

Neutral

(source)

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

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rs769823589

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over