chr10-102837300-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_000102.4(CYP17A1):​c.62G>T​(p.Arg21Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R21K) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CYP17A1
NM_000102.4 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.656

Publications

0 publications found
Variant links:
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]
CYP17A1 Gene-Disease associations (from GenCC):
  • congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency
    Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
  • 46,XY disorder of sex development due to isolated 17,20-lyase deficiency
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 48 curated pathogenic missense variants (we use a threshold of 10). The gene has 2 curated benign missense variants. Gene score misZ: 1.2356 (below the threshold of 3.09). Trascript score misZ: 1.3377 (below the threshold of 3.09). GenCC associations: The gene is linked to congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency, 46,XY disorder of sex development due to isolated 17,20-lyase deficiency.
BP4
Computational evidence support a benign effect (MetaRNN=0.20207477).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CYP17A1NM_000102.4 linkc.62G>T p.Arg21Met missense_variant Exon 1 of 8 ENST00000369887.4 NP_000093.1 P05093Q1HB44

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CYP17A1ENST00000369887.4 linkc.62G>T p.Arg21Met missense_variant Exon 1 of 8 1 NM_000102.4 ENSP00000358903.3 P05093

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1458484
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
725872
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33406
American (AMR)
AF:
0.00
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26122
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39674
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86182
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53414
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5760
European-Non Finnish (NFE)
AF:
9.02e-7
AC:
1
AN:
1108942
Other (OTH)
AF:
0.00
AC:
0
AN:
60264
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
16
DANN
Benign
0.93
DEOGEN2
Uncertain
0.53
.;.;D;.;.
Eigen
Benign
-0.72
Eigen_PC
Benign
-0.86
FATHMM_MKL
Benign
0.080
N
LIST_S2
Benign
0.76
T;T;T;T;T
M_CAP
Benign
0.080
D
MetaRNN
Benign
0.20
T;T;T;T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Uncertain
2.1
.;.;M;.;.
PhyloP100
-0.66
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-1.3
.;.;N;.;.
REVEL
Benign
0.18
Sift
Benign
0.094
.;.;T;.;.
Sift4G
Benign
0.097
.;.;T;.;.
Polyphen
0.99
.;.;D;.;.
Vest4
0.23
MutPred
0.47
Loss of glycosylation at P18 (P = 0.0778);Loss of glycosylation at P18 (P = 0.0778);Loss of glycosylation at P18 (P = 0.0778);Loss of glycosylation at P18 (P = 0.0778);Loss of glycosylation at P18 (P = 0.0778);
MVP
0.77
MPC
0.77
ClinPred
0.57
D
GERP RS
-3.8
PromoterAI
0.036
Neutral
Varity_R
0.045
gMVP
0.33
Mutation Taster
=91/9
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs61754263; hg19: chr10-104597057; API