rs17335568

chrX-7256772-G-AchrX-7256772-G-C

Variant summary

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

The NM_001320752.2(STS):c.138-470G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 110,253 control chromosomes in the GnomAD database, including 5,138 homozygotes. There are 11,018 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 0.35 (5138 hom., 11018 hem., cov: 22)
• Consequence: STS NM_001320752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370

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 (NFE) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STS	NM_001320752.2	c.138-470G>A		intron_variant		ENST00000674429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STS	ENST00000674429.1	c.138-470G>A		intron_variant			NM_001320752.2	P1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 38880 AN: 110201 Hom.: 5138 Cov.: 22 AF XY: 0.339 AC XY: 11020 AN XY: 32483

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.353 AC: 38873 AN: 110253 Hom.: 5138 Cov.: 22 AF XY: 0.339 AC XY: 11018 AN XY: 32545

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.369

Alfa AF: 0.359 Hom.: 3563

Bravo AF: 0.356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.5
Dann	Benign	0.44

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: rs17335568; hg19: chrX-7174813;