chr10-70883952-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM4PP5
The NM_000281.4(PCBD1):āc.313T>Cā(p.Ter105Glnext*?) variant causes a stop lost change. The variant allele was found at a frequency of 0.0000123 in 1,461,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000281.4 stop_lost
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PCBD1 | NM_000281.4 | c.313T>C | p.Ter105Glnext*? | stop_lost | Exon 4 of 4 | ENST00000299299.4 | NP_000272.1 | |
PCBD1 | NM_001289797.2 | c.166T>C | p.Ter56Glnext*? | stop_lost | Exon 4 of 4 | NP_001276726.1 | ||
PCBD1 | NM_001323004.2 | c.216+1200T>C | intron_variant | Intron 3 of 3 | NP_001309933.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250456Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135338
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461378Hom.: 0 Cov.: 35 AF XY: 0.0000124 AC XY: 9AN XY: 726886
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Pterin-4 alpha-carbinolamine dehydratase 1 deficiency Pathogenic:1Uncertain:1
This sequence change disrupts the translational stop signal of the PCBD1 mRNA. It is expected to extend the length of the PCBD1 protein by 14 additional amino acid residues. This variant is present in population databases (rs770334825, gnomAD 0.003%). This protein extension has been observed in individual(s) with clinical features of biopterin-deficient hyperphenylalaninemia (PMID: 24133926, 27246466). ClinVar contains an entry for this variant (Variation ID: 428616). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at