chr10-102835149-T-A

Variant names:

• chr10-102835149-T-A
• rs743575
• NM_000102.4:c.436+105A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000102.4(CYP17A1):​c.436+105A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000597 in 1,005,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000060 (0 hom.)
• Consequence: CYP17A1 NM_000102.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.415
• Publications: 12 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000102.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP17A1	NM_000102.4	MANE Select	c.436+105A>T		intron	N/A	NP_000093.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP17A1	ENST00000369887.4	TSL:1 MANE Select	c.436+105A>T		intron	N/A	ENSP00000358903.3
	CYP17A1	ENST00000639393.1	TSL:5	c.436+105A>T		intron	N/A	ENSP00000492651.1
	CYP17A1	ENST00000638971.1	TSL:5	c.436+105A>T		intron	N/A	ENSP00000492313.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000597 AC: 6 AN: 1005288 Hom.: 0 Cov.: 14 AF XY: 0.00000580 AC XY: 3 AN XY: 517444

African (AFR) AF: 0.00 AC: 0 AN: 24864

American (AMR) AF: 0.00 AC: 0 AN: 43420

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22784

East Asian (EAS) AF: 0.00 AC: 0 AN: 37484

South Asian (SAS) AF: 0.0000130 AC: 1 AN: 76692

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43486

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3736

European-Non Finnish (NFE) AF: 0.00000707 AC: 5 AN: 707360

Other (OTH) AF: 0.00 AC: 0 AN: 45462

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 515

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.6
DANN	Benign	0.76
PhyloP100		-0.41

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: rs743575; hg19: chr10-104594906;