rs1057517680
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5
The NM_176869.3(PPA2):c.318G>T(p.Met106Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000709 in 1,409,588 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: 31)
Exomes 𝑓: 0.0000071 ( 0 hom. )
Consequence
PPA2
NM_176869.3 missense
NM_176869.3 missense
Scores
7
8
4
Clinical Significance
Conservation
PhyloP100: 7.60
Genes affected
PPA2 (HGNC:28883): (inorganic pyrophosphatase 2) The protein encoded by this gene is localized to the mitochondrion, is highly similar to members of the inorganic pyrophosphatase (PPase) family, and contains the signature sequence essential for the catalytic activity of PPase. PPases catalyze the hydrolysis of pyrophosphate to inorganic phosphate, which is important for the phosphate metabolism of cells. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
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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, 0.751
PP5
?
Variant 4-105449353-C-A is Pathogenic according to our data. Variant chr4-105449353-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 372224.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PPA2 | NM_176869.3 | c.318G>T | p.Met106Ile | missense_variant | 4/12 | ENST00000341695.10 | |
PPA2 | NM_006903.4 | c.318G>T | p.Met106Ile | missense_variant | 4/11 | ||
PPA2 | NM_176866.2 | c.222+7328G>T | intron_variant | ||||
PPA2 | NM_176867.3 | c.157+24541G>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PPA2 | ENST00000341695.10 | c.318G>T | p.Met106Ile | missense_variant | 4/12 | 1 | NM_176869.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome AF: 0.00000709 AC: 10AN: 1409588Hom.: 0 Cov.: 27 AF XY: 0.00000853 AC XY: 6AN XY: 703608
GnomAD4 exome
AF:
AC:
10
AN:
1409588
Hom.:
Cov.:
27
AF XY:
AC XY:
6
AN XY:
703608
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Sudden cardiac failure, infantile Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 23, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M;.;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;.;T
Polyphen
P;B;.;.
Vest4
MutPred
Gain of methylation at K105 (P = 0.0391);Gain of methylation at K105 (P = 0.0391);.;.;
MVP
MPC
ClinPred
D
GERP RS
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