rs5934671

chrX-7205044-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001320752.2(STS):c.-5+14036C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 111,049 control chromosomes in the GnomAD database, including 3,333 homozygotes. There are 8,599 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 0.28 (3333 hom., 8599 hem., cov: 22)
• Consequence: STS NM_001320752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STS	NM_001320752.2	c.-5+14036C>G		intron_variant		ENST00000674429.1
STS	NM_001320750.3	c.32+14036C>G		intron_variant
STS	NM_001320751.2	c.32+14036C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STS	ENST00000674429.1	c.-5+14036C>G		intron_variant			NM_001320752.2	P1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 30786 AN: 110996 Hom.: 3339 Cov.: 22 AF XY: 0.259 AC XY: 8600 AN XY: 33248

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.0735

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.277 AC: 30768 AN: 111049 Hom.: 3333 Cov.: 22 AF XY: 0.258 AC XY: 8599 AN XY: 33311

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.0733

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.290

Alfa AF: 0.280 Hom.: 1763

Bravo AF: 0.275

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.73
Dann	Benign	0.52

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5934671; hg19: chrX-7123085;