rs17268974

Positions:

• chrX-7318929-T-A
• chrX-7318929-T-C
• chrX-7318929-T-G

Variant summary

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

The NM_001320752.2(STS):​c.1082-6410T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 110,835 control chromosomes in the GnomAD database, including 1,795 homozygotes. There are 6,291 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 0.20 (1795 hom., 6291 hem., cov: 22)
• Consequence: STS NM_001320752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.334

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STS	NM_001320752.2	c.1082-6410T>A		intron_variant		ENST00000674429.1	NP_001307681.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STS	ENST00000674429.1	c.1082-6410T>A		intron_variant			NM_001320752.2	ENSP00000501534.1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 21860 AN: 110778 Hom.: 1789 Cov.: 22 AF XY: 0.191 AC XY: 6291 AN XY: 33010

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.197 AC: 21866 AN: 110835 Hom.: 1795 Cov.: 22 AF XY: 0.190 AC XY: 6291 AN XY: 33077

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.197

Alfa AF: 0.188 Hom.: 1098

Bravo AF: 0.205

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.9
DANN	Benign	0.77

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: rs17268974; hg19: chrX-7236970;