rs12689028

Positions:

• chrX-7718359-T-C

Variant summary

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

The ENST00000664306.2(STS):​c.*84-14633T>C variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 111,287 control chromosomes in the GnomAD database, including 1,523 homozygotes. There are 4,766 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 0.15 (1523 hom., 4766 hem., cov: 23)
• Consequence: STS ENST00000664306.2 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STS	ENST00000664306.2	c.*84-14633T>C		intron_variant, NMD_transcript_variant				ENSP00000499549

Frequencies

GnomAD3 genomes AF: 0.146 AC: 16194 AN: 111233 Hom.: 1521 Cov.: 23 AF XY: 0.142 AC XY: 4751 AN XY: 33511

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.0161

Gnomad AMR AF: 0.0783

Gnomad ASJ AF: 0.0515

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0569

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.146 AC: 16212 AN: 111287 Hom.: 1523 Cov.: 23 AF XY: 0.142 AC XY: 4766 AN XY: 33575

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.0782

Gnomad4 ASJ AF: 0.0515

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.0569

Gnomad4 OTH AF: 0.134

Alfa AF: 0.0762 Hom.: 2504

Bravo AF: 0.156

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12689028; hg19: chrX-7686400;