rs1555890224
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The NM_016335.6(PRODH):āc.1418T>Cā(p.Met473Thr) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 5)
Exomes š: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PRODH
NM_016335.6 missense
NM_016335.6 missense
Scores
2
2
10
Clinical Significance
Conservation
PhyloP100: 5.63
Genes affected
PRODH (HGNC:9453): (proline dehydrogenase 1) This gene encodes a mitochondrial protein that catalyzes the first step in proline degradation. Mutations in this gene are associated with hyperprolinemia type 1 and susceptibility to schizophrenia 4 (SCZD4). This gene is located on chromosome 22q11.21, a region which has also been associated with the contiguous gene deletion syndromes, DiGeorge and CATCH22. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.777
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRODH | NM_016335.6 | c.1418T>C | p.Met473Thr | missense_variant | 11/14 | ENST00000357068.11 | |
PRODH | NM_001195226.2 | c.1094T>C | p.Met365Thr | missense_variant | 11/14 | ||
PRODH | NM_001368250.2 | c.1094T>C | p.Met365Thr | missense_variant | 11/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRODH | ENST00000357068.11 | c.1418T>C | p.Met473Thr | missense_variant | 11/14 | 1 | NM_016335.6 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 5
GnomAD3 genomes
?
Cov.:
5
GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 136254Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 71906
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
AC:
0
AN:
136254
Hom.:
Cov.:
0
AF XY:
AC XY:
0
AN XY:
71906
Gnomad4 AFR exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 OTH exome
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GnomAD4 genome ? Cov.: 5
GnomAD4 genome
?
Cov.:
5
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Proline dehydrogenase deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 12, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 529418). This variant has not been reported in the literature in individuals affected with PRODH-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 473 of the PRODH protein (p.Met473Thr). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;.;T;.
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
Sift4G
Benign
T;T;T;T
Polyphen
0.63
.;P;P;.
Vest4
MutPred
Loss of stability (P = 0.0636);.;.;Loss of stability (P = 0.0636);
MVP
MPC
0.42
ClinPred
D
GERP RS
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