rs104894144
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5
The NM_000102.4(CYP17A1):āc.985T>Gā(p.Tyr329Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,654 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 Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes š: 6.9e-7 ( 0 hom. )
Consequence
CYP17A1
NM_000102.4 missense
NM_000102.4 missense
Scores
2
8
9
Clinical Significance
Conservation
PhyloP100: 7.61
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]
WBP1L (HGNC:23510): (WW domain binding protein 1 like) Predicted to enable ubiquitin protein ligase binding activity. Predicted to act upstream of or within CXCL12-activated CXCR4 signaling pathway; hemopoiesis; and positive regulation of protein ubiquitination. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.918
PP5
Variant 10-102832665-A-C is Pathogenic according to our data. Variant chr10-102832665-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 1798.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CYP17A1 | NM_000102.4 | c.985T>G | p.Tyr329Asp | missense_variant | 6/8 | ENST00000369887.4 | NP_000093.1 | |
CYP17A1-AS1 | XR_428804.2 | n.-11A>C | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CYP17A1 | ENST00000369887.4 | c.985T>G | p.Tyr329Asp | missense_variant | 6/8 | 1 | NM_000102.4 | ENSP00000358903.3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.88e-7 AC: 1AN: 1453654Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1AN XY: 723746
GnomAD4 exome
AF:
AC:
1
AN:
1453654
Hom.:
Cov.:
28
AF XY:
AC XY:
1
AN XY:
723746
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
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 complete Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 2003 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Benign
DEOGEN2
Uncertain
.;.;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T;T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;L;.;.
PrimateAI
Benign
T
PROVEAN
Benign
.;.;N;.;.
REVEL
Uncertain
Sift
Uncertain
.;.;D;.;.
Sift4G
Uncertain
.;.;D;.;.
Polyphen
0.12
.;.;B;.;.
Vest4
0.76
MutPred
0.84
.;.;Gain of disorder (P = 0.009);.;Gain of disorder (P = 0.009);
MVP
0.85
MPC
0.57
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at