rs10521591

Variant names:

• chrX-7648514-C-T
• rs10521591
• ENST00000664306.2:n.*83+62187C>T

Variant summary

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

The ENST00000664306.2(STS):​n.*83+62187C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0264 in 111,600 control chromosomes in the GnomAD database, including 83 homozygotes. There are 811 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 0.026 (83 hom., 811 hem., cov: 22)
• Consequence: STS ENST00000664306.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STS	ENST00000664306.2	n.*83+62187C>T		intron_variant	Intron 11 of 12			ENSP00000499549.2

Frequencies

GnomAD3 genomes AF: 0.0264 AC: 2950 AN: 111546 Hom.: 84 Cov.: 22 AF XY: 0.0240 AC XY: 812 AN XY: 33766

Gnomad AFR AF: 0.0822

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0148

Gnomad ASJ AF: 0.0454

Gnomad EAS AF: 0.000281

Gnomad SAS AF: 0.000756

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0340

Gnomad NFE AF: 0.00181

Gnomad OTH AF: 0.0319

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0264 AC: 2949 AN: 111600 Hom.: 83 Cov.: 22 AF XY: 0.0240 AC XY: 811 AN XY: 33830

Gnomad4 AFR AF: 0.0820

Gnomad4 AMR AF: 0.0148

Gnomad4 ASJ AF: 0.0454

Gnomad4 EAS AF: 0.000282

Gnomad4 SAS AF: 0.000759

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00181

Gnomad4 OTH AF: 0.0315

Alfa AF: 0.0214 Hom.: 67

Bravo AF: 0.0319

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.033
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10521591; hg19: chrX-7566555;