X-7318929-T-A

Variant names:

• chrX-7318929-T-A
• rs17268974
• NM_001320752.2:c.1082-6410T>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.1082-6410T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 110,835 control chromosomes in the GnomAD database, including 1,795 homozygotes. There are 6,291 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 0.20 (1795 hom., 6291 hem., cov: 22)
• Consequence: STS NM_001320752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.334
• Publications: 9 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: Orphanet, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, Genomics England PanelApp

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.382 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STS	NM_001320752.2	MANE Select	c.1082-6410T>A		intron	N/A	NP_001307681.2	A0A590UJL0
	STS	NM_001320750.3		c.1118-6410T>A		intron	N/A	NP_001307679.1
	STS	NM_001320751.2		c.1118-6410T>A		intron	N/A	NP_001307680.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STS	ENST00000674429.1	MANE Select	c.1082-6410T>A		intron	N/A	ENSP00000501534.1	A0A590UJL0
	STS	ENST00000217961.5	TSL:1	c.1082-6410T>A		intron	N/A	ENSP00000217961.5	A0A590UJL0
	STS	ENST00000666110.2		c.1082-6410T>A		intron	N/A	ENSP00000499472.2	A0A590UJL0

Frequencies

GnomAD3 genomes AF: 0.197 AC: 21860 AN: 110778 Hom.: 1789 Cov.: 22

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.197 AC: 21866 AN: 110835 Hom.: 1795 Cov.: 22 AF XY: 0.190 AC XY: 6291 AN XY: 33077

African (AFR) AF: 0.101 AC: 3093 AN: 30615

American (AMR) AF: 0.239 AC: 2480 AN: 10380

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 638 AN: 2625

East Asian (EAS) AF: 0.400 AC: 1376 AN: 3440

South Asian (SAS) AF: 0.203 AC: 530 AN: 2605

European-Finnish (FIN) AF: 0.212 AC: 1250 AN: 5889

Middle Eastern (MID) AF: 0.161 AC: 35 AN: 217

European-Non Finnish (NFE) AF: 0.225 AC: 11907 AN: 52872

Other (OTH) AF: 0.197 AC: 299 AN: 1519

Alfa AF: 0.188 Hom.: 1098

Bravo AF: 0.205

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.9
DANN	Benign	0.77
PhyloP100		0.33
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: rs17268974; hg19: chrX-7236970;