rs869025293
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5
The NM_015160.3(PMPCA):c.1543G>A(p.Gly515Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
PMPCA
NM_015160.3 missense
NM_015160.3 missense
Scores
4
10
5
Clinical Significance
Conservation
PhyloP100: 8.01
Genes affected
PMPCA (HGNC:18667): (peptidase, mitochondrial processing subunit alpha) The protein encoded by this gene is found in the mitochondrion, where it represents the alpha subunit of a proteolytic heterodimer. This heterodimer is responsible for cleaving the transit peptide from nuclear-encoded mitochondrial proteins. Defects in this gene are a cause of spinocerebellar ataxia, autosomal recessive 2. [provided by RefSeq, Mar 2016]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.755
PP5
Variant 9-136423229-G-A is Pathogenic according to our data. Variant chr9-136423229-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 221565.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-136423229-G-A is described in UniProt as null. Variant chr9-136423229-G-A is described in UniProt as null. Variant chr9-136423229-G-A is described in UniProt as null.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PMPCA | NM_015160.3 | c.1543G>A | p.Gly515Arg | missense_variant | 13/13 | ENST00000371717.8 | NP_055975.1 | |
PMPCA | NM_001282946.2 | c.1243G>A | p.Gly415Arg | missense_variant | 13/13 | NP_001269875.1 | ||
PMPCA | NM_001282944.2 | c.1150G>A | p.Gly384Arg | missense_variant | 12/12 | NP_001269873.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.00000800 AC: 2AN: 250022Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135502
GnomAD3 exomes
AF:
AC:
2
AN:
250022
Hom.:
AF XY:
AC XY:
2
AN XY:
135502
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: 0.00000342 AC: 5AN: 1461056Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4AN XY: 726830
GnomAD4 exome
AF:
AC:
5
AN:
1461056
Hom.:
Cov.:
33
AF XY:
AC XY:
4
AN XY:
726830
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 Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Autosomal recessive spinocerebellar ataxia 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 12, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MutPred
Gain of helix (P = 0.0117);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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