chr14-54842552-A-AAT
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2
The NM_000161.3(GCH1):c.*1464_*1465insAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0163 in 153,894 control chromosomes in the GnomAD database, including 38 homozygotes. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.016 ( 37 hom., cov: 32)
Exomes 𝑓: 0.015 ( 1 hom. )
Consequence
GCH1
NM_000161.3 3_prime_UTR
NM_000161.3 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.0760
Genes affected
GCH1 (HGNC:4193): (GTP cyclohydrolase 1) This gene encodes a member of the GTP cyclohydrolase family. The encoded protein is the first and rate-limiting enzyme in tetrahydrobiopterin (BH4) biosynthesis, catalyzing the conversion of GTP into 7,8-dihydroneopterin triphosphate. BH4 is an essential cofactor required by aromatic amino acid hydroxylases as well as nitric oxide synthases. Mutations in this gene are associated with malignant hyperphenylalaninemia and dopa-responsive dystonia. Several alternatively spliced transcript variants encoding different isoforms have been described; however, not all variants give rise to a functional enzyme. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP6
?
Variant 14-54842552-A-AAT is Benign according to our data. Variant chr14-54842552-A-AAT is described in ClinVar as [Likely_benign]. Clinvar id is 313364.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0163 (2483/152272) while in subpopulation SAS AF= 0.0482 (232/4814). AF 95% confidence interval is 0.0431. There are 37 homozygotes in gnomad4. There are 1342 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 38 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GCH1 | NM_000161.3 | c.*1464_*1465insAT | 3_prime_UTR_variant | 6/6 | ENST00000491895.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GCH1 | ENST00000491895.7 | c.*1464_*1465insAT | 3_prime_UTR_variant | 6/6 | 1 | NM_000161.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0163 AC: 2485AN: 152154Hom.: 38 Cov.: 32
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GnomAD4 exome AF: 0.0154 AC: 25AN: 1622Hom.: 1 Cov.: 0 AF XY: 0.0169 AC XY: 15AN XY: 886
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
GTP cyclohydrolase I deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Dopa-responsive dystonia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at