rs10521591

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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]

STS Gene-Disease associations (from GenCC):

• recessive X-linked ichthyosis

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, PanelApp Australia

ENSG00000296839 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000664306.2. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STS	ENST00000664306.2		n.*83+62187C>T		intron	N/A	ENSP00000499549.2	A0A590UJT4
	ENSG00000296839	ENST00000742933.1		n.503-29819C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0264 AC: 2950 AN: 111546 Hom.: 84 Cov.: 22

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

African (AFR) AF: 0.0820 AC: 2520 AN: 30723

American (AMR) AF: 0.0148 AC: 155 AN: 10477

Ashkenazi Jewish (ASJ) AF: 0.0454 AC: 120 AN: 2644

East Asian (EAS) AF: 0.000282 AC: 1 AN: 3549

South Asian (SAS) AF: 0.000759 AC: 2 AN: 2636

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6039

Middle Eastern (MID) AF: 0.0326 AC: 7 AN: 215

European-Non Finnish (NFE) AF: 0.00181 AC: 96 AN: 53109

Other (OTH) AF: 0.0315 AC: 48 AN: 1522

Alfa AF: 0.0214 Hom.: 67

Bravo AF: 0.0319

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.033
DANN	Benign	0.67
PhyloP100		-2.5

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10521591;

hg19: chrX-7566555;