chr11-72293433-G-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate
The NM_030813.6(CLPB):c.2058C>T(p.Asp686=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000223 in 1,614,182 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 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000022 ( 0 hom. )
Consequence
CLPB
NM_030813.6 synonymous
NM_030813.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.29
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 Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
Variant 11-72293433-G-A is Benign according to our data. Variant chr11-72293433-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1126257.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-72293433-G-A is described in Lovd as [Likely_benign].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLPB | NM_030813.6 | c.2058C>T | p.Asp686= | synonymous_variant | 17/17 | ENST00000294053.9 | |
CLPB | NM_001258392.3 | c.1968C>T | p.Asp656= | synonymous_variant | 16/16 | ENST00000538039.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLPB | ENST00000294053.9 | c.2058C>T | p.Asp686= | synonymous_variant | 17/17 | 1 | NM_030813.6 | P4 | |
CLPB | ENST00000538039.6 | c.1968C>T | p.Asp656= | synonymous_variant | 16/16 | 2 | NM_001258392.3 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152186Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251402Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135896
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GnomAD4 exome AF: 0.0000219 AC: 32AN: 1461878Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 15AN XY: 727242
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152304Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74464
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
3-methylglutaconic aciduria, type VIIB Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 13, 2022 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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