Genetic Variant ENST00000369887:c.*165delT (chr10-102830536-GA-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS1

The ENST00000369887(CYP17A1):c.*165delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00274 in 480,616 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 0 hom. )

Consequence

CYP17A1
ENST00000369887 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0520

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 links:

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]

WBP1L links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00128 (187/146102) while in subpopulation SAS AF= 0.0039 (18/4610). AF 95% confidence interval is 0.00252. There are 0 homozygotes in gnomad4. There are 105 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP17A1	NM_000102.4 link	c.*165delT		3_prime_UTR_variant	Exon 8 of 8	ENST00000369887.4	NP_000093.1	P05093Q1HB44

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP17A1	ENST00000369887 link	c.*165delT		3_prime_UTR_variant	Exon 8 of 8	1	NM_000102.4	ENSP00000358903.3		P05093

Frequencies

GnomAD3 genomes

AF:

0.00125

AC:

183

AN:

146030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00190

Gnomad AMI

AF:

0.0292

Gnomad AMR

AF:

0.00198

Gnomad ASJ

AF:

0.00265

Gnomad EAS

AF:

0.000794

Gnomad SAS

AF:

0.00389

Gnomad FIN

AF:

0.000550

Gnomad MID

AF:

0.00323

Gnomad NFE

AF:

0.000212

Gnomad OTH

AF:

0.000500

GnomAD4 exome

AF:

0.00337

AC:

1128

AN:

334514

Hom.:

Cov.:

AF XY:

0.00354

AC XY:

625

AN XY:

176726

show subpopulations

Gnomad4 AFR exome

AF:

0.00448

Gnomad4 AMR exome

AF:

0.00344

Gnomad4 ASJ exome

AF:

0.00612

Gnomad4 EAS exome

AF:

0.00326

Gnomad4 SAS exome

AF:

0.00469

Gnomad4 FIN exome

AF:

0.00288

Gnomad4 NFE exome

AF:

0.00304

Gnomad4 OTH exome

AF:

0.00311

GnomAD4 genome

AF:

0.00128

AC:

187

AN:

146102

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

105

AN XY:

70912

show subpopulations

Gnomad4 AFR

AF:

0.00200

Gnomad4 AMR

AF:

0.00198

Gnomad4 ASJ

AF:

0.00265

Gnomad4 EAS

AF:

0.000796

Gnomad4 SAS

AF:

0.00390

Gnomad4 FIN

AF:

0.000550

Gnomad4 NFE

AF:

0.000212

Gnomad4 OTH

AF:

0.000495

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over