rs5978405

chrX-7291386-T-AchrX-7291386-T-CchrX-7291386-T-G

Variant summary

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

The NM_001320752.2(STS):c.944-13660T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 110,640 control chromosomes in the GnomAD database, including 5,163 homozygotes. There are 11,268 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 (5163 hom., 11268 hem., cov: 23)
• Consequence: STS NM_001320752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STS	NM_001320752.2	c.944-13660T>A		intron_variant		ENST00000674429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STS	ENST00000674429.1	c.944-13660T>A		intron_variant			NM_001320752.2	P1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 39157 AN: 110584 Hom.: 5163 Cov.: 23 AF XY: 0.343 AC XY: 11267 AN XY: 32870

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.374

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.354 AC: 39152 AN: 110640 Hom.: 5163 Cov.: 23 AF XY: 0.342 AC XY: 11268 AN XY: 32936

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.372

Alfa AF: 0.198 Hom.: 961

Bravo AF: 0.356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	6.4
Dann	Benign	0.72

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: rs5978405; hg19: chrX-7209427;