rs4403552

Variant names:

• chrX-7325263-G-A
• rs4403552
• NM_001320752.2:c.1082-76G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-7325263-G-A
• chrX-7325263-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

STS Gene-Disease associations (from GenCC):

• recessive X-linked ichthyosis

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320752.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STS	NM_001320752.2	MANE Select	c.1082-76G>A		intron	N/A	NP_001307681.2	A0A590UJL0
	STS	NM_001320750.3		c.1118-76G>A		intron	N/A	NP_001307679.1
	STS	NM_001320751.2		c.1118-76G>A		intron	N/A	NP_001307680.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STS	ENST00000674429.1	MANE Select	c.1082-76G>A		intron	N/A	ENSP00000501534.1	A0A590UJL0
	STS	ENST00000217961.5	TSL:1	c.1082-76G>A		intron	N/A	ENSP00000217961.5	A0A590UJL0
	STS	ENST00000666110.2		c.1082-76G>A		intron	N/A	ENSP00000499472.2	A0A590UJL0

Frequencies

GnomAD3 genomes AF: 0.230 AC: 25490 AN: 110894 Hom.: 2149 Cov.: 22

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

African (AFR) AF: 0.245 AC: 5922 AN: 24123

American (AMR) AF: 0.286 AC: 8845 AN: 30945

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 2722 AN: 18376

East Asian (EAS) AF: 0.357 AC: 10235 AN: 28671

South Asian (SAS) AF: 0.180 AC: 8934 AN: 49694

European-Finnish (FIN) AF: 0.244 AC: 9480 AN: 38813

Middle Eastern (MID) AF: 0.176 AC: 687 AN: 3903

European-Non Finnish (NFE) AF: 0.226 AC: 168096 AN: 744768

Other (OTH) AF: 0.238 AC: 10056 AN: 42188

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

African (AFR) AF: 0.237 AC: 7243 AN: 30512

American (AMR) AF: 0.234 AC: 2442 AN: 10457

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 397 AN: 2643

East Asian (EAS) AF: 0.386 AC: 1344 AN: 3482

South Asian (SAS) AF: 0.190 AC: 495 AN: 2604

European-Finnish (FIN) AF: 0.228 AC: 1347 AN: 5909

Middle Eastern (MID) AF: 0.248 AC: 53 AN: 214

European-Non Finnish (NFE) AF: 0.218 AC: 11539 AN: 52947

Other (OTH) AF: 0.246 AC: 371 AN: 1507

Alfa AF: 0.222 Hom.: 16714

Bravo AF: 0.239

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0010
DANN	Benign	0.38
PhyloP100		-5.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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