chrX-7648514-C-T

Position:

• chrX-7648514-C-T

Variant summary

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

The ENST00000664306.2(STS):​c.*83+62187C>T variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0264 in 111,600 control chromosomes in the GnomAD database, including 83 homozygotes. There are 811 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 0.026 (83 hom., 811 hem., cov: 22)
• Consequence: STS ENST00000664306.2 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0794 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+62187C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0264 AC: 2950 AN: 111546 Hom.: 84 Cov.: 22 AF XY: 0.0240 AC XY: 812 AN XY: 33766

Gnomad AFR AF: 0.0822

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0148

Gnomad ASJ AF: 0.0454

Gnomad EAS AF: 0.000281

Gnomad SAS AF: 0.000756

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0340

Gnomad NFE AF: 0.00181

Gnomad OTH AF: 0.0319

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

GnomAD4 genome AF: 0.0264 AC: 2949 AN: 111600 Hom.: 83 Cov.: 22 AF XY: 0.0240 AC XY: 811 AN XY: 33830

Gnomad4 AFR AF: 0.0820

Gnomad4 AMR AF: 0.0148

Gnomad4 ASJ AF: 0.0454

Gnomad4 EAS AF: 0.000282

Gnomad4 SAS AF: 0.000759

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00181

Gnomad4 OTH AF: 0.0315

Alfa AF: 0.0214 Hom.: 67

Bravo AF: 0.0319

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.033
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10521591; hg19: chrX-7566555;