14-54844023-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_000161.3(GCH1):āc.747G>Cā(p.Arg249Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R249G) has been classified as Uncertain significance.
Frequency
Consequence
NM_000161.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GCH1 | NM_000161.3 | c.747G>C | p.Arg249Ser | missense_variant | 6/6 | ENST00000491895.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GCH1 | ENST00000491895.7 | c.747G>C | p.Arg249Ser | missense_variant | 6/6 | 1 | NM_000161.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 249020Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134796
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461846Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727232
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Dystonia, dopa-responsive, with or without hyperphenylalaninemia, autosomal recessive Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 1999 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 08, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at