19-6361727-G-A
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_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
NM_006012.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0710
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
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/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CLPP | NM_006012.4 | c.153G>A | p.Thr51Thr | synonymous_variant | 1/6 | ENST00000245816.11 | NP_006003.1 | |
CLPP | XM_047439486.1 | c.153G>A | p.Thr51Thr | synonymous_variant | 1/5 | XP_047295442.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CLPP | ENST00000245816.11 | c.153G>A | p.Thr51Thr | synonymous_variant | 1/6 | 1 | NM_006012.4 | ENSP00000245816.3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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33
GnomAD3 exomes AF: 0.0000450 AC: 5AN: 111080Hom.: 0 AF XY: 0.0000667 AC XY: 4AN XY: 60010
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GnomAD4 exome AF: 0.0000303 AC: 41AN: 1354944Hom.: 0 Cov.: 32 AF XY: 0.0000376 AC XY: 25AN XY: 665262
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GnomAD4 genome Cov.: 33
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33
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 02, 2016 | 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
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Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at