rs141458508
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6_Very_StrongBP7
The NM_030813.6(CLPB):c.1794G>A(p.Thr598=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000608 in 1,614,166 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00064 ( 1 hom. )
Consequence
CLPB
NM_030813.6 synonymous
NM_030813.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.74
Genes affected
CLPB (HGNC:30664): (ClpB family mitochondrial disaggregase) This gene belongs to the ATP-ases associated with diverse cellular activities (AAA+) superfamily. Members of this superfamily form ring-shaped homo-hexamers and have highly conserved ATPase domains that are involved in various processes including DNA replication, protein degradation and reactivation of misfolded proteins. All members of this family hydrolyze ATP through their AAA+ domains and use the energy generated through ATP hydrolysis to exert mechanical force on their substrates. In addition to an AAA+ domain, the protein encoded by this gene contains a C-terminal D2 domain, which is characteristic of the AAA+ subfamily of Caseinolytic peptidases to which this protein belongs. It cooperates with Hsp70 in the disaggregation of protein aggregates. Allelic variants of this gene are associated with 3-methylglutaconic aciduria, which causes cataracts and neutropenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
?
Variant 11-72294103-C-T is Benign according to our data. Variant chr11-72294103-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 476193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.74 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLPB | NM_030813.6 | c.1794G>A | p.Thr598= | synonymous_variant | 16/17 | ENST00000294053.9 | |
CLPB | NM_001258392.3 | c.1704G>A | p.Thr568= | synonymous_variant | 15/16 | ENST00000538039.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLPB | ENST00000294053.9 | c.1794G>A | p.Thr598= | synonymous_variant | 16/17 | 1 | NM_030813.6 | P4 | |
CLPB | ENST00000538039.6 | c.1704G>A | p.Thr568= | synonymous_variant | 15/16 | 2 | NM_001258392.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000328 AC: 50AN: 152240Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000379 AC: 95AN: 250796Hom.: 0 AF XY: 0.000347 AC XY: 47AN XY: 135564
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GnomAD4 exome AF: 0.000638 AC: 932AN: 1461808Hom.: 1 Cov.: 32 AF XY: 0.000624 AC XY: 454AN XY: 727190
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GnomAD4 genome ? AF: 0.000328 AC: 50AN: 152358Hom.: 0 Cov.: 33 AF XY: 0.000268 AC XY: 20AN XY: 74504
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2022 | CLPB: BP4, BP7 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 28, 2019 | - - |
3-methylglutaconic aciduria, type VIIB Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Computational scores
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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