rs184218784
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_016335.6(PRODH):c.1729C>T(p.Arg577Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_016335.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRODH | NM_016335.6 | c.1729C>T | p.Arg577Trp | missense_variant | Exon 14 of 14 | ENST00000357068.11 | NP_057419.5 | |
PRODH | NM_001195226.2 | c.1405C>T | p.Arg469Trp | missense_variant | Exon 14 of 14 | NP_001182155.2 | ||
PRODH | NM_001368250.2 | c.1405C>T | p.Arg469Trp | missense_variant | Exon 14 of 14 | NP_001355179.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRODH | ENST00000357068.11 | c.1729C>T | p.Arg577Trp | missense_variant | Exon 14 of 14 | 1 | NM_016335.6 | ENSP00000349577.6 | ||
ENSG00000283809 | ENST00000638240.1 | c.513+2221G>A | intron_variant | Intron 4 of 5 | 5 | ENSP00000492446.1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 6AN: 31724Hom.: 3 Cov.: 0 FAILED QC
GnomAD3 exomes AF: 0.000422 AC: 69AN: 163548Hom.: 0 AF XY: 0.000347 AC XY: 30AN XY: 86556
GnomAD4 exome AF: 0.000129 AC: 65AN: 504300Hom.: 28 Cov.: 0 AF XY: 0.000101 AC XY: 25AN XY: 248360
GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000189 AC: 6AN: 31724Hom.: 3 Cov.: 0 AF XY: 0.000261 AC XY: 4AN XY: 15312
ClinVar
Submissions by phenotype
not provided Uncertain:1
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function -
Proline dehydrogenase deficiency Uncertain:1
This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 577 of the PRODH protein (p.Arg577Trp). This variant is present in population databases (rs184218784, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with PRODH-related conditions. ClinVar contains an entry for this variant (Variation ID: 1214571). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt PRODH protein function with a negative predictive value of 80%. 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. -
Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Proline dehydrogenase deficiency;C1833247:Schizophrenia 4 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at