rs281875319
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_006907.4(PYCR1):c.743G>A(p.Gly248Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,612,692 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
PYCR1
NM_006907.4 missense
NM_006907.4 missense
Scores
4
12
2
Clinical Significance
Conservation
PhyloP100: 7.68
Genes affected
PYCR1 (HGNC:9721): (pyrroline-5-carboxylate reductase 1) This gene encodes an enzyme that catalyzes the NAD(P)H-dependent conversion of pyrroline-5-carboxylate to proline. This enzyme may also play a physiologic role in the generation of NADP(+) in some cell types. The protein forms a homopolymer and localizes to the mitochondrion. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM1
?
In a hotspot region, there are 5 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 6 uncertain in NM_006907.4
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PYCR1 | NM_006907.4 | c.743G>A | p.Gly248Glu | missense_variant | 6/7 | ENST00000329875.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PYCR1 | ENST00000329875.13 | c.743G>A | p.Gly248Glu | missense_variant | 6/7 | 1 | NM_006907.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152264Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000242 AC: 6AN: 247888Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134556
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460428Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 726440
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152264Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74390
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ClinVar
Significance: Uncertain significance
Submissions summary: Pathogenic:1Uncertain:1Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1Other:1
not provided, no classification provided | literature only | UniProtKB/Swiss-Prot | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jul 22, 2020 | - - |
PYCR1-related de Barsy syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 2011 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
D;.;.;D;.;D;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.;M;.;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;.;.;D;.;.
REVEL
Pathogenic
Sift
Uncertain
D;D;.;.;D;.;.
Sift4G
Uncertain
D;D;D;D;D;.;D
Polyphen
D;.;.;D;.;.;.
Vest4
MutPred
Gain of solvent accessibility (P = 0.012);Gain of solvent accessibility (P = 0.012);.;Gain of solvent accessibility (P = 0.012);.;.;Gain of solvent accessibility (P = 0.012);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at