rs6639811

Positions:

• chrX-7297762-A-G
• chrX-7297762-A-T

Variant summary

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

The NM_001320752.2(STS):​c.944-7284A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 110,886 control chromosomes in the GnomAD database, including 5,308 homozygotes. There are 11,538 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 0.36 (5308 hom., 11538 hem., cov: 23)
• Consequence: STS NM_001320752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.367

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) 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.944-7284A>G		intron_variant		ENST00000674429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STS	ENST00000674429.1	c.944-7284A>G		intron_variant			NM_001320752.2	P1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 39910 AN: 110833 Hom.: 5308 Cov.: 23 AF XY: 0.349 AC XY: 11541 AN XY: 33115

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.390

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.360 AC: 39902 AN: 110886 Hom.: 5308 Cov.: 23 AF XY: 0.348 AC XY: 11538 AN XY: 33178

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.357

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.377

Alfa AF: 0.347 Hom.: 2832

Bravo AF: 0.363

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.33
DANN	Benign	0.23

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: rs6639811; hg19: chrX-7215803;