rs923644

chrX-7643222-G-AchrX-7643222-G-C

Variant summary

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

The ENST00000664306.2(STS):c.*83+56895G>A variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0401 in 110,399 control chromosomes in the GnomAD database, including 180 homozygotes. There are 1,233 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 0.040 (180 hom., 1233 hem., cov: 22)
• Consequence: STS ENST00000664306.2 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STS	ENST00000664306.2	c.*83+56895G>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0400 AC: 4412 AN: 110343 Hom.: 176 Cov.: 22 AF XY: 0.0377 AC XY: 1230 AN XY: 32593

Gnomad AFR AF: 0.0676

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0368

Gnomad ASJ AF: 0.0534

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.0805

Gnomad FIN AF: 0.0121

Gnomad MID AF: 0.0678

Gnomad NFE AF: 0.0130

Gnomad OTH AF: 0.0474

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

GnomAD4 genome AF: 0.0401 AC: 4424 AN: 110399 Hom.: 180 Cov.: 22 AF XY: 0.0378 AC XY: 1233 AN XY: 32659

Gnomad4 AFR AF: 0.0675

Gnomad4 AMR AF: 0.0373

Gnomad4 ASJ AF: 0.0534

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.0792

Gnomad4 FIN AF: 0.0121

Gnomad4 NFE AF: 0.0131

Gnomad4 OTH AF: 0.0561

Alfa AF: 0.00873 Hom.: 35

Bravo AF: 0.0464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	8.8
Dann	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs923644; hg19: chrX-7561263;