rs12689028

Variant names:

• chrX-7718359-T-C
• rs12689028
• ENST00000664306.2:n.*84-14633T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000664306.2(STS):​n.*84-14633T>C variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111
• Publications: 1 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: G2P, Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STS	ENST00000664306.2	n.*84-14633T>C		intron_variant	Intron 11 of 12			ENSP00000499549.2

Frequencies

GnomAD3 genomes AF: 0.146 AC: 16194 AN: 111233 Hom.: 1521 Cov.: 23

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

African (AFR) AF: 0.339 AC: 10354 AN: 30546

American (AMR) AF: 0.0782 AC: 822 AN: 10515

Ashkenazi Jewish (ASJ) AF: 0.0515 AC: 136 AN: 2641

East Asian (EAS) AF: 0.149 AC: 523 AN: 3514

South Asian (SAS) AF: 0.186 AC: 496 AN: 2672

European-Finnish (FIN) AF: 0.104 AC: 622 AN: 5995

Middle Eastern (MID) AF: 0.146 AC: 31 AN: 212

European-Non Finnish (NFE) AF: 0.0569 AC: 3017 AN: 53015

Other (OTH) AF: 0.134 AC: 200 AN: 1494

Alfa AF: 0.0977 Hom.: 3877

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
PhyloP100		-0.11

Splicing

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

Other links and lift over

dbSNP: rs12689028; hg19: chrX-7686400;