rs727519

Positions:

• chrX-7214204-G-C

Variant summary

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

The NM_001320752.2(STS):​c.-5+23196G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 111,777 control chromosomes in the GnomAD database, including 2,523 homozygotes. There are 8,188 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 0.23 (2523 hom., 8188 hem., cov: 23)
• Consequence: STS NM_001320752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.841

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STS	NM_001320752.2	c.-5+23196G>C		intron_variant		ENST00000674429.1
STS	NM_001320750.3	c.32+23196G>C		intron_variant
STS	NM_001320751.2	c.32+23196G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STS	ENST00000674429.1	c.-5+23196G>C		intron_variant			NM_001320752.2	P1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 26246 AN: 111725 Hom.: 2525 Cov.: 23 AF XY: 0.241 AC XY: 8175 AN XY: 33957

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.0775

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.235 AC: 26253 AN: 111777 Hom.: 2523 Cov.: 23 AF XY: 0.241 AC XY: 8188 AN XY: 34019

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.369

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.238

Alfa AF: 0.260 Hom.: 1660

Bravo AF: 0.239

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs727519; hg19: chrX-7132245;