rs4403552

Positions:

• chrX-7325263-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001320752.2(STS):​c.1082-76G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,092,430 control chromosomes in the GnomAD database, including 20,724 homozygotes. There are 73,710 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (2150 hom., 7324 hem., cov: 22)
  • Exomes 𝑓: 0.23 (18574 hom. 66386 hem.)
• Consequence: STS NM_001320752.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.56

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant X-7325263-G-A is Benign according to our data. Variant chrX-7325263-G-A is described in ClinVar as [Benign]. Clinvar id is 1236792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STS	NM_001320752.2	c.1082-76G>A		intron_variant		ENST00000674429.1	NP_001307681.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STS	ENST00000674429.1	c.1082-76G>A		intron_variant			NM_001320752.2	ENSP00000501534	P1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 25490 AN: 110894 Hom.: 2149 Cov.: 22 AF XY: 0.221 AC XY: 7327 AN XY: 33136

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.241

GnomAD4 exome AF: 0.229 AC: 224977 AN: 981481 Hom.: 18574 AF XY: 0.230 AC XY: 66386 AN XY: 289109

Gnomad4 AFR exome AF: 0.245

Gnomad4 AMR exome AF: 0.286

Gnomad4 ASJ exome AF: 0.148

Gnomad4 EAS exome AF: 0.357

Gnomad4 SAS exome AF: 0.180

Gnomad4 FIN exome AF: 0.244

Gnomad4 NFE exome AF: 0.226

Gnomad4 OTH exome AF: 0.238

GnomAD4 genome AF: 0.230 AC: 25479 AN: 110949 Hom.: 2150 Cov.: 22 AF XY: 0.221 AC XY: 7324 AN XY: 33201

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.246

Alfa AF: 0.219 Hom.: 11672

Bravo AF: 0.239

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 20, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0010
DANN	Benign	0.38

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: rs4403552; hg19: chrX-7243304; COSMIC: COSV54268478;