rs17268988

chrX-7336440-C-G

Variant summary

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

The NM_001320752.2(STS):c.1363+2333C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 111,181 control chromosomes in the GnomAD database, including 2,102 homozygotes. There are 7,081 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 0.22 (2102 hom., 7081 hem., cov: 23)
• Consequence: STS NM_001320752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.709

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STS	NM_001320752.2	c.1363+2333C>G		intron_variant		ENST00000674429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STS	ENST00000674429.1	c.1363+2333C>G		intron_variant			NM_001320752.2	P1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 24335 AN: 111131 Hom.: 2103 Cov.: 23 AF XY: 0.212 AC XY: 7077 AN XY: 33367

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.333

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.219 AC: 24330 AN: 111181 Hom.: 2102 Cov.: 23 AF XY: 0.212 AC XY: 7081 AN XY: 33427

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.227

Alfa AF: 0.243 Hom.: 1485

Bravo AF: 0.208

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.13
Dann	Benign	0.42

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: rs17268988; hg19: chrX-7254481;