19-6361634-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.60G>A(p.Leu20=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 1,426,386 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: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000016 ( 0 hom. )
Consequence
CLPP
NM_006012.4 synonymous
NM_006012.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0140
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=-0.79).
BP6
Variant 19-6361634-G-A is Benign according to our data. Variant chr19-6361634-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1967215.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.014 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLPP | NM_006012.4 | c.60G>A | p.Leu20= | synonymous_variant | 1/6 | ENST00000245816.11 | |
CLPP | XM_047439486.1 | c.60G>A | p.Leu20= | synonymous_variant | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLPP | ENST00000245816.11 | c.60G>A | p.Leu20= | synonymous_variant | 1/6 | 1 | NM_006012.4 | P1 | |
ENST00000595644.1 | n.35+481C>T | intron_variant, non_coding_transcript_variant | 4 | ||||||
CLPP | ENST00000596070.1 | n.70G>A | non_coding_transcript_exon_variant | 1/5 | 5 | ||||
CLPP | ENST00000594780.1 | upstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152226Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000157 AC: 2AN: 1274160Hom.: 0 Cov.: 31 AF XY: 0.00000162 AC XY: 1AN XY: 618702
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152226Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74366
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 12, 2022 | - - |
Computational scores
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Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at