rs5933863

Variant names:

• chrX-7352653-G-A
• rs5933863
• NM_001320752.2:c.*2392G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001320752.2(STS):​c.*2392G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 111,167 control chromosomes in the GnomAD database, including 619 homozygotes. There are 3,365 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 0.11 (619 hom., 3365 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: STS NM_001320752.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.236
• Publications: 6 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: G2P, Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.16 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STS	NM_001320752.2	MANE Select	c.*2392G>A		3_prime_UTR	Exon 11 of 11	NP_001307681.2
	STS	NM_001320750.3		c.*2392G>A		3_prime_UTR	Exon 11 of 11	NP_001307679.1
	STS	NM_001320751.2		c.*2392G>A		3_prime_UTR	Exon 12 of 12	NP_001307680.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STS	ENST00000674429.1	MANE Select	c.*2392G>A		3_prime_UTR	Exon 11 of 11	ENSP00000501534.1
	STS	ENST00000217961.5	TSL:1	c.*2392G>A		3_prime_UTR	Exon 10 of 10	ENSP00000217961.5
	STS	ENST00000666110.2		c.*2392G>A		3_prime_UTR	Exon 11 of 11	ENSP00000499472.2

Frequencies

GnomAD3 genomes AF: 0.107 AC: 11874 AN: 111110 Hom.: 621 Cov.: 23

Gnomad AFR AF: 0.0244

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.0824

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.127

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.107 AC: 11862 AN: 111167 Hom.: 619 Cov.: 23 AF XY: 0.101 AC XY: 3365 AN XY: 33379

African (AFR) AF: 0.0244 AC: 750 AN: 30721

American (AMR) AF: 0.0822 AC: 854 AN: 10391

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 308 AN: 2641

East Asian (EAS) AF: 0.00 AC: 0 AN: 3551

South Asian (SAS) AF: 0.0124 AC: 33 AN: 2655

European-Finnish (FIN) AF: 0.151 AC: 885 AN: 5871

Middle Eastern (MID) AF: 0.175 AC: 38 AN: 217

European-Non Finnish (NFE) AF: 0.163 AC: 8642 AN: 52933

Other (OTH) AF: 0.124 AC: 188 AN: 1511

Alfa AF: 0.135 Hom.: 2677

Bravo AF: 0.0987

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.24
PhyloP100		0.24
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: rs5933863; hg19: chrX-7270694;