rs5934913

Variant names:

• chrX-7294236-G-A
• rs5934913
• NM_001320752.2:c.944-10810G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001320752.2(STS):​c.944-10810G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 109,618 control chromosomes in the GnomAD database, including 7,742 homozygotes. There are 13,283 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 0.43 (7742 hom., 13283 hem., cov: 22)
• Consequence: STS NM_001320752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109
• Publications: 3 publications found

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]

STS Gene-Disease associations (from GenCC):

• recessive X-linked ichthyosis

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STS	NM_001320752.2	c.944-10810G>A		intron_variant	Intron 7 of 10	ENST00000674429.1	NP_001307681.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STS	ENST00000674429.1	c.944-10810G>A		intron_variant	Intron 7 of 10		NM_001320752.2	ENSP00000501534.1

Frequencies

GnomAD3 genomes AF: 0.432 AC: 47341 AN: 109573 Hom.: 7742 Cov.: 22

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.432 AC: 47348 AN: 109618 Hom.: 7742 Cov.: 22 AF XY: 0.415 AC XY: 13283 AN XY: 31996

African (AFR) AF: 0.519 AC: 15639 AN: 30136

American (AMR) AF: 0.371 AC: 3826 AN: 10303

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 948 AN: 2620

East Asian (EAS) AF: 0.405 AC: 1380 AN: 3408

South Asian (SAS) AF: 0.227 AC: 585 AN: 2573

European-Finnish (FIN) AF: 0.383 AC: 2181 AN: 5694

Middle Eastern (MID) AF: 0.392 AC: 80 AN: 204

European-Non Finnish (NFE) AF: 0.412 AC: 21634 AN: 52515

Other (OTH) AF: 0.434 AC: 648 AN: 1493

Alfa AF: 0.409 Hom.: 4030

Bravo AF: 0.441

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.68
DANN	Benign	0.71
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5934913; hg19: chrX-7212277;