22-18913186-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_016335.6(PRODH):c.1792C>T(p.Arg598Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R598H) has been classified as Uncertain significance.
Frequency
Consequence
NM_016335.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRODH | NM_016335.6 | c.1792C>T | p.Arg598Cys | missense_variant | 14/14 | ENST00000357068.11 | |
PRODH | NM_001195226.2 | c.1468C>T | p.Arg490Cys | missense_variant | 14/14 | ||
PRODH | NM_001368250.2 | c.1468C>T | p.Arg490Cys | missense_variant | 14/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRODH | ENST00000357068.11 | c.1792C>T | p.Arg598Cys | missense_variant | 14/14 | 1 | NM_016335.6 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 0
GnomAD3 exomes AF: 0.0000256 AC: 4AN: 155988Hom.: 0 AF XY: 0.0000363 AC XY: 3AN XY: 82688
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000826 AC: 3AN: 363154Hom.: 1 Cov.: 0 AF XY: 0.0000167 AC XY: 3AN XY: 179984
GnomAD4 genome ? Cov.: 0
ClinVar
Submissions by phenotype
Proline dehydrogenase deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 12, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 598 of the PRODH protein (p.Arg598Cys). 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 output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with PRODH-related conditions. This variant is present in population databases (rs755449569, gnomAD 0.008%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at