rs3923341

Variant names:

• chrX-7300859-C-T
• rs3923341
• NM_001320752.2:c.944-4187C>T

Variant summary

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

The NM_001320752.2(STS):​c.944-4187C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 109,995 control chromosomes in the GnomAD database, including 6,406 homozygotes. There are 12,273 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 0.40 (6406 hom., 12273 hem., cov: 22)
• Consequence: STS NM_001320752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.651
• 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: 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STS	NM_001320752.2	c.944-4187C>T		intron_variant	Intron 7 of 10	ENST00000674429.1	NP_001307681.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STS	ENST00000674429.1	c.944-4187C>T		intron_variant	Intron 7 of 10		NM_001320752.2	ENSP00000501534.1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 43567 AN: 109941 Hom.: 6408 Cov.: 22

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.397

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.396 AC: 43584 AN: 109995 Hom.: 6406 Cov.: 22 AF XY: 0.380 AC XY: 12273 AN XY: 32329

African (AFR) AF: 0.428 AC: 12937 AN: 30215

American (AMR) AF: 0.357 AC: 3673 AN: 10278

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 939 AN: 2627

East Asian (EAS) AF: 0.403 AC: 1395 AN: 3460

South Asian (SAS) AF: 0.223 AC: 583 AN: 2614

European-Finnish (FIN) AF: 0.372 AC: 2139 AN: 5745

Middle Eastern (MID) AF: 0.383 AC: 82 AN: 214

European-Non Finnish (NFE) AF: 0.395 AC: 20802 AN: 52665

Other (OTH) AF: 0.405 AC: 610 AN: 1506

Alfa AF: 0.382 Hom.: 3198

Bravo AF: 0.404

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.11
DANN	Benign	0.22
PhyloP100		-0.65
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: rs3923341; hg19: chrX-7218900;