X-7251505-G-T

Variant names:

• chrX-7251505-G-T
• rs5934770
• NM_001320752.2:c.-4-1691G>T

Variant summary

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

The NM_001320752.2(STS):​c.-4-1691G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0924 in 110,520 control chromosomes in the GnomAD database, including 461 homozygotes. There are 2,868 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 0.092 (461 hom., 2868 hem., cov: 22)
• Consequence: STS NM_001320752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118
• Publications: 2 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)

ENSG00000293893 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320752.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STS	NM_001320752.2	MANE Select	c.-4-1691G>T		intron	N/A	NP_001307681.2
	STS	NM_001320750.3		c.33-1691G>T		intron	N/A	NP_001307679.1
	STS	NM_001320751.2		c.33-1691G>T		intron	N/A	NP_001307680.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STS	ENST00000674429.1	MANE Select	c.-4-1691G>T		intron	N/A	ENSP00000501534.1
	STS	ENST00000217961.5	TSL:1	c.-4-1691G>T		intron	N/A	ENSP00000217961.5
	STS	ENST00000666110.2		c.-4-1691G>T		intron	N/A	ENSP00000499472.2

Frequencies

GnomAD3 genomes AF: 0.0925 AC: 10223 AN: 110468 Hom.: 461 Cov.: 22

Gnomad AFR AF: 0.0213

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.0668

Gnomad ASJ AF: 0.0776

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0135

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.0924 AC: 10216 AN: 110520 Hom.: 461 Cov.: 22 AF XY: 0.0875 AC XY: 2868 AN XY: 32764

African (AFR) AF: 0.0213 AC: 650 AN: 30469

American (AMR) AF: 0.0666 AC: 688 AN: 10325

Ashkenazi Jewish (ASJ) AF: 0.0776 AC: 204 AN: 2628

East Asian (EAS) AF: 0.00 AC: 0 AN: 3485

South Asian (SAS) AF: 0.0128 AC: 33 AN: 2574

European-Finnish (FIN) AF: 0.135 AC: 787 AN: 5822

Middle Eastern (MID) AF: 0.101 AC: 22 AN: 217

European-Non Finnish (NFE) AF: 0.142 AC: 7503 AN: 52822

Other (OTH) AF: 0.112 AC: 168 AN: 1502

Alfa AF: 0.114 Hom.: 8950

Bravo AF: 0.0843

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.84
DANN	Benign	0.46
PhyloP100		-0.12
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: rs5934770; hg19: chrX-7169546;