X-7251477-T-C

Position:

• chrX-7251477-T-C

Variant summary

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

The NM_001320752.2(STS):​c.-4-1719T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 108,724 control chromosomes in the GnomAD database, including 5,127 homozygotes. There are 10,699 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 0.35 (5127 hom., 10699 hem., cov: 21)
• Consequence: STS NM_001320752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STS	NM_001320752.2	c.-4-1719T>C		intron_variant		ENST00000674429.1	NP_001307681.2
STS	NM_000351.7	c.-4-1719T>C		intron_variant			NP_000342.3
STS	NM_001320750.3	c.33-1719T>C		intron_variant			NP_001307679.1
STS	NM_001320751.2	c.33-1719T>C		intron_variant			NP_001307680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STS	ENST00000674429.1	c.-4-1719T>C		intron_variant			NM_001320752.2	ENSP00000501534	P1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 38528 AN: 108675 Hom.: 5127 Cov.: 21 AF XY: 0.344 AC XY: 10703 AN XY: 31113

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.381

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.354 AC: 38519 AN: 108724 Hom.: 5127 Cov.: 21 AF XY: 0.343 AC XY: 10699 AN XY: 31172

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.401

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.377

Alfa AF: 0.366 Hom.: 4271

Bravo AF: 0.356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.37
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs5934769; hg19: chrX-7169518;