rs886037932
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_ModeratePP5_Moderate
The NM_013328.4(PYCR2):c.773T>C(p.Val258Ala) 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 Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
PYCR2
NM_013328.4 missense
NM_013328.4 missense
Scores
5
11
1
Clinical Significance
Conservation
PhyloP100: 7.34
Genes affected
PYCR2 (HGNC:30262): (pyrroline-5-carboxylate reductase 2) This gene belongs to the pyrroline-5-carboxylate reductase family. The encoded mitochondrial protein catalyzes the conversion of pyrroline-5-carboxylate to proline, which is the last step in proline biosynthesis. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Nov 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM1
?
In a helix (size 19) in uniprot entity P5CR2_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_013328.4
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.924
PP5
?
Variant 1-225921232-A-G is Pathogenic according to our data. Variant chr1-225921232-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 254248.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PYCR2 | NM_013328.4 | c.773T>C | p.Val258Ala | missense_variant | 6/7 | ENST00000343818.11 | |
PYCR2 | NM_001271681.2 | c.551T>C | p.Val184Ala | missense_variant | 5/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PYCR2 | ENST00000343818.11 | c.773T>C | p.Val258Ala | missense_variant | 6/7 | 1 | NM_013328.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hypomyelinating leukodystrophy 10 Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 16, 2016 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Centre for Inherited Metabolic Diseases, Karolinska University Hospital | Mar 20, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;.;D
REVEL
Pathogenic
Sift
Uncertain
D;.;.;D
Sift4G
Uncertain
D;D;D;D
Polyphen
1.0
.;.;.;D
Vest4
MutPred
0.78
.;.;.;Loss of stability (P = 0.0437);
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