rs869025292
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5
The NM_015160.3(PMPCA):c.287C>T(p.Ser96Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PMPCA
NM_015160.3 missense
NM_015160.3 missense
Scores
12
5
2
Clinical Significance
Conservation
PhyloP100: 7.46
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.908
PP5
?
Variant 9-136412502-C-T is Pathogenic according to our data. Variant chr9-136412502-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 221564.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PMPCA | NM_015160.3 | c.287C>T | p.Ser96Leu | missense_variant | 3/13 | ENST00000371717.8 | |
PMPCA | XM_005266059.4 | c.287C>T | p.Ser96Leu | missense_variant | 3/12 | ||
PMPCA | NM_001282944.2 | c.-12C>T | 5_prime_UTR_variant | 3/12 | |||
PMPCA | NM_001282946.2 | c.-12C>T | 5_prime_UTR_variant | 3/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PMPCA | ENST00000371717.8 | c.287C>T | p.Ser96Leu | missense_variant | 3/13 | 1 | NM_015160.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1415996Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0AN XY: 706046
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1415996
Hom.:
Cov.:
26
AF XY:
AC XY:
0
AN XY:
706046
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
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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
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
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
DS_AG_spliceai
Position offset: 3
Find out detailed SpliceAI scores and Pangolin per-transcript scores at