rs5933863

Positions:

• chrX-7352653-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001320752.2(STS):​c.*2392G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 111,167 control chromosomes in the GnomAD database, including 619 homozygotes. There are 3,365 hemizygotes in GnomAD. 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: 𝑓 0.11 (619 hom., 3365 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: STS NM_001320752.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.236

Genes affected

STS (HGNC:11425): (steroid sulfatase) This gene encodes a multi-pass membrane protein that is localized to the endoplasmic reticulum. It belongs to the sulfatase family and hydrolyzes several 3-beta-hydroxysteroid sulfates, which serve as metabolic precursors for estrogens, androgens, and cholesterol. Mutations in this gene are associated with X-linked ichthyosis (XLI). Alternatively spliced transcript variants resulting from the use of different promoters have been described for this gene (PMID:17601726). [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STS	NM_001320752.2	c.*2392G>A		3_prime_UTR_variant	11/11	ENST00000674429.1	NP_001307681.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STS	ENST00000674429.1	c.*2392G>A		3_prime_UTR_variant	11/11		NM_001320752.2	ENSP00000501534	P1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 11874 AN: 111110 Hom.: 621 Cov.: 23 AF XY: 0.101 AC XY: 3365 AN XY: 33312

Gnomad AFR AF: 0.0244

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.0824

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.127

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.107 AC: 11862 AN: 111167 Hom.: 619 Cov.: 23 AF XY: 0.101 AC XY: 3365 AN XY: 33379

Gnomad4 AFR AF: 0.0244

Gnomad4 AMR AF: 0.0822

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0124

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.124

Alfa AF: 0.136 Hom.: 2521

Bravo AF: 0.0987

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.24

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

LitVar

Other links and lift over

dbSNP: rs5933863; hg19: chrX-7270694;