rs11095437

Positions:

• chrX-7247450-T-C

Variant summary

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

The NM_001320752.2(STS):​c.-4-5746T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 111,308 control chromosomes in the GnomAD database, including 2,059 homozygotes. There are 6,624 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 (2059 hom., 6624 hem., cov: 23)
• Consequence: STS NM_001320752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STS	NM_001320752.2	c.-4-5746T>C		intron_variant		ENST00000674429.1	NP_001307681.2
STS	NM_000351.7	c.-4-5746T>C		intron_variant			NP_000342.3
STS	NM_001320750.3	c.33-5746T>C		intron_variant			NP_001307679.1
STS	NM_001320751.2	c.33-5746T>C		intron_variant			NP_001307680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STS	ENST00000674429.1	c.-4-5746T>C		intron_variant			NM_001320752.2	ENSP00000501534	P1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 22142 AN: 111253 Hom.: 2061 Cov.: 23 AF XY: 0.198 AC XY: 6615 AN XY: 33447

Gnomad AFR AF: 0.0530

Gnomad AMI AF: 0.0806

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.144

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.199 AC: 22145 AN: 111308 Hom.: 2059 Cov.: 23 AF XY: 0.198 AC XY: 6624 AN XY: 33512

Gnomad4 AFR AF: 0.0528

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.212

Alfa AF: 0.242 Hom.: 14094

Bravo AF: 0.207

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.9
DANN	Benign	0.25

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: rs11095437; hg19: chrX-7165491;