rs7058445

Variant names:

• chrX-7254467-T-C
• rs7058445
• NM_001320752.2:c.137+1131T>C

Variant summary

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

The NM_001320752.2(STS):​c.137+1131T>C 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 110,079 control chromosomes in the GnomAD database, including 2,939 homozygotes. There are 8,429 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 (2939 hom., 8429 hem., cov: 22)
• Consequence: STS NM_001320752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.601
• 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: 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STS	NM_001320752.2	c.137+1131T>C		intron_variant	Intron 3 of 10	ENST00000674429.1	NP_001307681.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STS	ENST00000674429.1	c.137+1131T>C		intron_variant	Intron 3 of 10		NM_001320752.2	ENSP00000501534.1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 28711 AN: 110038 Hom.: 2941 Cov.: 22

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.0792

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.163

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.261 AC: 28714 AN: 110079 Hom.: 2939 Cov.: 22 AF XY: 0.260 AC XY: 8429 AN XY: 32365

African (AFR) AF: 0.157 AC: 4768 AN: 30357

American (AMR) AF: 0.419 AC: 4302 AN: 10269

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 659 AN: 2631

East Asian (EAS) AF: 0.306 AC: 1065 AN: 3479

South Asian (SAS) AF: 0.382 AC: 980 AN: 2567

European-Finnish (FIN) AF: 0.262 AC: 1496 AN: 5711

Middle Eastern (MID) AF: 0.160 AC: 35 AN: 219

European-Non Finnish (NFE) AF: 0.284 AC: 14975 AN: 52674

Other (OTH) AF: 0.255 AC: 380 AN: 1490

Alfa AF: 0.283 Hom.: 9949

Bravo AF: 0.268

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.37
DANN	Benign	0.49
PhyloP100		-0.60
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: rs7058445; hg19: chrX-7172508;