rs61754263

Variant names:

• chr10-102837300-C-A
• NM_000102.4:c.62G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-102837300-C-A
• chr10-102837300-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 15/21 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.656

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20207477).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP17A1	NM_000102.4	c.62G>T	p.Arg21Met	missense_variant	Exon 1 of 8	ENST00000369887.4	NP_000093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP17A1	ENST00000369887.4	c.62G>T	p.Arg21Met	missense_variant	Exon 1 of 8	1	NM_000102.4	ENSP00000358903.3

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.00

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;.;.
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
Varity_R		0.045
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-104597057;