rs77345581
Positions:
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_030813.6(CLPB):c.1519C>T(p.Leu507=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000139 in 1,614,216 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00013 ( 2 hom. )
Consequence
CLPB
NM_030813.6 synonymous
NM_030813.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.92
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
Variant 11-72295549-G-A is Benign according to our data. Variant chr11-72295549-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 386086.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.92 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 2 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLPB | NM_030813.6 | c.1519C>T | p.Leu507= | synonymous_variant | 13/17 | ENST00000294053.9 | |
CLPB | NM_001258392.3 | c.1429C>T | p.Leu477= | synonymous_variant | 12/16 | ENST00000538039.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLPB | ENST00000294053.9 | c.1519C>T | p.Leu507= | synonymous_variant | 13/17 | 1 | NM_030813.6 | P4 | |
CLPB | ENST00000538039.6 | c.1429C>T | p.Leu477= | synonymous_variant | 12/16 | 2 | NM_001258392.3 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000230 AC: 35AN: 152228Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
35
AN:
152228
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000553 AC: 139AN: 251266Hom.: 1 AF XY: 0.000508 AC XY: 69AN XY: 135820
GnomAD3 exomes
AF:
AC:
139
AN:
251266
Hom.:
AF XY:
AC XY:
69
AN XY:
135820
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000131 AC: 191AN: 1461870Hom.: 2 Cov.: 31 AF XY: 0.000106 AC XY: 77AN XY: 727234
GnomAD4 exome
AF:
AC:
191
AN:
1461870
Hom.:
Cov.:
31
AF XY:
AC XY:
77
AN XY:
727234
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000223 AC: 34AN: 152346Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18AN XY: 74494
GnomAD4 genome
AF:
AC:
34
AN:
152346
Hom.:
Cov.:
33
AF XY:
AC XY:
18
AN XY:
74494
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
14
AN:
3478
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 23, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
3-methylglutaconic aciduria, type VIIB Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 26, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at