X-7248171-C-A

Variant names:

• chrX-7248171-C-A
• rs2024159
• NM_001320752.2:c.-4-5025C>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.-4-5025C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 111,250 control chromosomes in the GnomAD database, including 2,937 homozygotes. There are 8,743 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 0.26 (2937 hom., 8743 hem., cov: 23)
• Consequence: STS NM_001320752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246
• Publications: 2 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

ENSG00000293893 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.41 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.-4-5025C>A		intron	N/A	NP_001307681.2	A0A590UJL0
	STS	NM_001320750.3		c.33-5025C>A		intron	N/A	NP_001307679.1
	STS	NM_001320751.2		c.33-5025C>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.-4-5025C>A		intron	N/A	ENSP00000501534.1	A0A590UJL0
	STS	ENST00000217961.5	TSL:1	c.-4-5025C>A		intron	N/A	ENSP00000217961.5	A0A590UJL0
	STS	ENST00000666110.2		c.-4-5025C>A		intron	N/A	ENSP00000499472.2	A0A590UJL0

Frequencies

GnomAD3 genomes AF: 0.261 AC: 29023 AN: 111195 Hom.: 2939 Cov.: 23

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.0791

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.261 AC: 29032 AN: 111250 Hom.: 2937 Cov.: 23 AF XY: 0.261 AC XY: 8743 AN XY: 33480

African (AFR) AF: 0.156 AC: 4800 AN: 30744

American (AMR) AF: 0.420 AC: 4380 AN: 10418

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 661 AN: 2643

East Asian (EAS) AF: 0.307 AC: 1078 AN: 3508

South Asian (SAS) AF: 0.373 AC: 984 AN: 2637

European-Finnish (FIN) AF: 0.272 AC: 1615 AN: 5927

Middle Eastern (MID) AF: 0.161 AC: 35 AN: 217

European-Non Finnish (NFE) AF: 0.284 AC: 15042 AN: 52964

Other (OTH) AF: 0.254 AC: 383 AN: 1509

Alfa AF: 0.281 Hom.: 2431

Bravo AF: 0.268

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.67
DANN	Benign	0.76
PhyloP100		-0.25
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: rs2024159; hg19: chrX-7166212;