rs3970559
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PS1_ModerateBP4_StrongBS1BS2
The NM_016335.6(PRODH):c.1357C>T(p.Arg453Cys) 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 Likely benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely pathogenic in UniProt.
Frequency
Consequence
NM_016335.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRODH | NM_016335.6 | c.1357C>T | p.Arg453Cys | missense_variant | Exon 11 of 14 | ENST00000357068.11 | NP_057419.5 | |
PRODH | NM_001195226.2 | c.1033C>T | p.Arg345Cys | missense_variant | Exon 11 of 14 | NP_001182155.2 | ||
PRODH | NM_001368250.2 | c.1033C>T | p.Arg345Cys | missense_variant | Exon 11 of 14 | NP_001355179.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRODH | ENST00000357068.11 | c.1357C>T | p.Arg453Cys | missense_variant | Exon 11 of 14 | 1 | NM_016335.6 | ENSP00000349577.6 | ||
ENSG00000283809 | ENST00000638240.1 | c.513+7358G>A | intron_variant | Intron 4 of 5 | 5 | ENSP00000492446.1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 332AN: 18570Hom.: 12 Cov.: 4 FAILED QC
GnomAD3 exomes AF: 0.0108 AC: 2704AN: 249400Hom.: 37 AF XY: 0.0106 AC XY: 1427AN XY: 134932
GnomAD4 exome AF: 0.0125 AC: 2640AN: 211074Hom.: 181 Cov.: 0 AF XY: 0.0121 AC XY: 1348AN XY: 111248
GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0180 AC: 335AN: 18618Hom.: 12 Cov.: 4 AF XY: 0.0183 AC XY: 152AN XY: 8320
ClinVar
Submissions by phenotype
Proline dehydrogenase deficiency Pathogenic:1Benign:1
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not specified Benign:2
BS1, BP6; This alteration has an allele frequency that is greater than expected for the associated disease, and was reported as a benign/likely benign alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory). -
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 3% in African population, >1% in most other populations. In addition, no clearly associated clinical manifestations -
Schizophrenia 4 Other:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at