rs1407920390
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PM1PM2PP3_StrongPP5_Very_Strong
The NM_000320.3(QDPR):c.344C>T(p.Ser115Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,614,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. S115S) has been classified as Benign.
Frequency
Consequence
NM_000320.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
QDPR | NM_000320.3 | c.344C>T | p.Ser115Leu | missense_variant | 4/7 | ENST00000281243.10 | NP_000311.2 | |
QDPR | NM_001306140.2 | c.251C>T | p.Ser84Leu | missense_variant | 3/6 | NP_001293069.1 | ||
QDPR | NR_156494.2 | n.380C>T | non_coding_transcript_exon_variant | 4/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
QDPR | ENST00000281243.10 | c.344C>T | p.Ser115Leu | missense_variant | 4/7 | 1 | NM_000320.3 | ENSP00000281243.5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251154Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135732
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461866Hom.: 0 Cov.: 35 AF XY: 0.00000688 AC XY: 5AN XY: 727230
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74352
ClinVar
Submissions by phenotype
Dihydropteridine reductase deficiency Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Pathology and Clinical Laboratory Medicine, King Fahad Medical City | - | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 06, 2023 | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 115 of the QDPR protein (p.Ser115Leu). This variant is present in population databases (no rsID available, gnomAD 0.002%). For these reasons, this variant has been classified as Pathogenic. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 459896). This missense change has been observed in individual(s) with BH4 deficiency (PMID: 26006720). - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Feb 21, 2023 | Observed with a second QDPR variant in a patient with BH4-deficient hyperphenylalaninemia in published literature, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes (Gundorova et al., 2021); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 33152132, 27527004, 33903016, 26006720, 27246466, 33822819) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at