rs6163

Variant names:

• chr10-102837167-C-A
• rs6163
• NM_000102.4:c.195G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-102837167-C-A
• chr10-102837167-C-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000102.4(CYP17A1):​c.195G>T​(p.Ser65Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 1,589,132 control chromosomes in the GnomAD database, including 117,961 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S65S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.39 (11751 hom., cov: 31)
  • Exomes 𝑓: 0.38 (106210 hom.)
• Consequence: CYP17A1 NM_000102.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.0410
• Publications: 80 publications found

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 10-102837167-C-A is Benign according to our data. Variant chr10-102837167-C-A is described in ClinVar as Benign. ClinVar VariationId is 298624.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.041 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP17A1	NM_000102.4	c.195G>T	p.Ser65Ser	synonymous_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.195G>T	p.Ser65Ser	synonymous_variant	Exon 1 of 8	1	NM_000102.4	ENSP00000358903.3

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59297 AN: 151854 Hom.: 11733 Cov.: 31

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.390

GnomAD2 exomes AF: 0.397 AC: 99954 AN: 251462 AF XY: 0.395

Gnomad AFR exome AF: 0.368

Gnomad AMR exome AF: 0.396

Gnomad ASJ exome AF: 0.394

Gnomad EAS exome AF: 0.567

Gnomad FIN exome AF: 0.365

Gnomad NFE exome AF: 0.392

Gnomad OTH exome AF: 0.394

GnomAD4 exome AF: 0.382 AC: 548921 AN: 1437162 Hom.: 106210 Cov.: 27 AF XY: 0.382 AC XY: 273833 AN XY: 716492

African (AFR) AF: 0.366 AC: 12062 AN: 32938

American (AMR) AF: 0.401 AC: 17908 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 10065 AN: 25964

East Asian (EAS) AF: 0.507 AC: 20035 AN: 39544

South Asian (SAS) AF: 0.363 AC: 31156 AN: 85770

European-Finnish (FIN) AF: 0.368 AC: 19638 AN: 53408

Middle Eastern (MID) AF: 0.392 AC: 2241 AN: 5722

European-Non Finnish (NFE) AF: 0.379 AC: 412623 AN: 1089500

Other (OTH) AF: 0.389 AC: 23193 AN: 59624

GnomAD4 genome AF: 0.391 AC: 59361 AN: 151970 Hom.: 11751 Cov.: 31 AF XY: 0.388 AC XY: 28836 AN XY: 74288

African (AFR) AF: 0.370 AC: 15338 AN: 41446

American (AMR) AF: 0.395 AC: 6025 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1384 AN: 3470

East Asian (EAS) AF: 0.562 AC: 2894 AN: 5150

South Asian (SAS) AF: 0.352 AC: 1699 AN: 4822

European-Finnish (FIN) AF: 0.354 AC: 3740 AN: 10554

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.400 AC: 27167 AN: 67956

Other (OTH) AF: 0.392 AC: 824 AN: 2104

Alfa AF: 0.391 Hom.: 41179

Bravo AF: 0.394

EpiCase AF: 0.387

EpiControl AF: 0.390

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 02, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Deficiency of steroid 17-alpha-monooxygenase Benign:3

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.1
DANN	Benign	0.49
PhyloP100		-0.041
PromoterAI		-0.025	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6163; hg19: chr10-104596924; COSMIC: COSV64004805; COSMIC: COSV64004805;