10-102830743-G-A
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PS1_ModeratePM2PM5PP3_StrongPP5_Very_Strong
The NM_000102.4(CYP17A1):c.1486C>T(p.Arg496Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,158 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 (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R496H) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000102.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CYP17A1 | NM_000102.4 | c.1486C>T | p.Arg496Cys | missense_variant | 8/8 | ENST00000369887.4 | NP_000093.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CYP17A1 | ENST00000369887.4 | c.1486C>T | p.Arg496Cys | missense_variant | 8/8 | 1 | NM_000102.4 | ENSP00000358903.3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1450158Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0AN XY: 721450
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Deficiency of steroid 17-alpha-monooxygenase Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Juno Genomics, Hangzhou Juno Genomics, Inc | - | PM2_Supporting+PP3+PP4+PM3_Strong+PS3_Supporting - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Aug 31, 2022 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 18, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 496 of the CYP17A1 protein (p.Arg496Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with congenital adrenal hyperplasia (PMID: 1515452, 9888582). ClinVar contains an entry for this variant (Variation ID: 1524567). 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. Experimental studies have shown that this missense change affects CYP17A1 function (PMID: 1515452). This variant disrupts the p.Arg496 amino acid residue in CYP17A1. Other variant(s) that disrupt this residue have been observed in individuals with CYP17A1-related conditions (PMID: 10720067, 16483711), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at