10-102830536-GAA-GAAAA

Variant names:

• chr10-102830536-G-GAA
• rs45455494
• NM_000102.4:c.*164_*165dupTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000102.4(CYP17A1):​c.*164_*165dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYP17A1 NM_000102.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520
• Publications: 0 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]

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP17A1	NM_000102.4	MANE Select	c.*164_*165dupTT		3_prime_UTR	Exon 8 of 8	NP_000093.1	Q1HB44

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP17A1	ENST00000369887.4	TSL:1 MANE Select	c.*164_*165dupTT		3_prime_UTR	Exon 8 of 8	ENSP00000358903.3	P05093
	CYP17A1	ENST00000960119.1		c.*164_*165dupTT		splice_region	Exon 8 of 8	ENSP00000630178.1
	CYP17A1	ENST00000960121.1		c.*164_*165dupTT		splice_region	Exon 8 of 8	ENSP00000630180.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 146044 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000144 AC: 49 AN: 339792 Hom.: 0 Cov.: 3 AF XY: 0.000162 AC XY: 29 AN XY: 179494

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000210 AC: 2 AN: 9544

American (AMR) AF: 0.0000678 AC: 1 AN: 14750

Ashkenazi Jewish (ASJ) AF: 0.0000954 AC: 1 AN: 10480

East Asian (EAS) AF: 0.000217 AC: 5 AN: 23064

South Asian (SAS) AF: 0.0000574 AC: 2 AN: 34844

European-Finnish (FIN) AF: 0.0000450 AC: 1 AN: 22212

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1486

European-Non Finnish (NFE) AF: 0.000137 AC: 28 AN: 203832

Other (OTH) AF: 0.000460 AC: 9 AN: 19580

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 146044 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 70832

African (AFR) AF: 0.00 AC: 0 AN: 39936

American (AMR) AF: 0.00 AC: 0 AN: 14650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3396

East Asian (EAS) AF: 0.00 AC: 0 AN: 5040

South Asian (SAS) AF: 0.00 AC: 0 AN: 4622

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9096

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66102

Other (OTH) AF: 0.00 AC: 0 AN: 2002

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.052

Splicing

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

Other links and lift over

dbSNP: rs45455494; hg19: chr10-104590293;