15-74337977-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_000781.3(CYP11A1):c.1561C>T(p.Gln521*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,680 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000781.3 stop_gained
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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CYP11A1 | NM_000781.3 | c.1561C>T | p.Gln521* | stop_gained | Exon 9 of 9 | ENST00000268053.11 | NP_000772.2 | |
CYP11A1 | NM_001099773.2 | c.1087C>T | p.Gln363* | stop_gained | Exon 9 of 9 | NP_001093243.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251462Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135906
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461680Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727152
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant summary: CYP11A1 c.1561C>T (p.Gln521X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein. The variant allele was found at a frequency of 1.2e-05 in 251462 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1561C>T in individuals affected with Congenital Adrenal Hyperplasia and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at