rs3923341

Positions:

• chrX-7300859-C-T

Variant summary

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

The NM_001320752.2(STS):​c.944-4187C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 109,995 control chromosomes in the GnomAD database, including 6,406 homozygotes. There are 12,273 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 0.40 (6406 hom., 12273 hem., cov: 22)
• Consequence: STS NM_001320752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.651

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STS	NM_001320752.2	c.944-4187C>T		intron_variant		ENST00000674429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STS	ENST00000674429.1	c.944-4187C>T		intron_variant			NM_001320752.2	P1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 43567 AN: 109941 Hom.: 6408 Cov.: 22 AF XY: 0.380 AC XY: 12254 AN XY: 32265

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.397

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.396 AC: 43584 AN: 109995 Hom.: 6406 Cov.: 22 AF XY: 0.380 AC XY: 12273 AN XY: 32329

Gnomad4 AFR AF: 0.428

Gnomad4 AMR AF: 0.357

Gnomad4 ASJ AF: 0.357

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.405

Alfa AF: 0.382 Hom.: 3198

Bravo AF: 0.404

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.11
DANN	Benign	0.22

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: rs3923341; hg19: chrX-7218900;