rs786205062
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_000102.4(CYP17A1):c.206_230del(p.Gly69AlafsTer26) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,450,102 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
CYP17A1
NM_000102.4 frameshift
NM_000102.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.50
Genes affected
CYP17A1 (HGNC:2593): (cytochrome P450 family 17 subfamily A member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum. It has both 17alpha-hydroxylase and 17,20-lyase activities and is a key enzyme in the steroidogenic pathway that produces progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens. Mutations in this gene are associated with isolated steroid-17 alpha-hydroxylase deficiency, 17-alpha-hydroxylase/17,20-lyase deficiency, pseudohermaphroditism, and adrenal hyperplasia. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 10-102837131-GCCGACAATCACTGTAGTCTTGGTGC-G is Pathogenic according to our data. Variant chr10-102837131-GCCGACAATCACTGTAGTCTTGGTGC-G is described in ClinVar as [Pathogenic]. Clinvar id is 1795.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP17A1 | NM_000102.4 | c.206_230del | p.Gly69AlafsTer26 | frameshift_variant | 1/8 | ENST00000369887.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP17A1 | ENST00000369887.4 | c.206_230del | p.Gly69AlafsTer26 | frameshift_variant | 1/8 | 1 | NM_000102.4 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome AF: 6.90e-7 AC: 1AN: 1450102Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 722150
GnomAD4 exome
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722150
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
17-alpha-hydroxylase/17,20-lyase deficiency, combined partial Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 2002 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at