X-7234072-G-A

Variant names:

• chrX-7234072-G-A
• rs1000900
• NM_001320752.2:c.-4-19124G>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.-4-19124G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 111,060 control chromosomes in the GnomAD database, including 2,521 homozygotes. There are 7,922 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 0.23 (2521 hom., 7922 hem., cov: 23)
• Consequence: STS NM_001320752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.548
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.398 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.-4-19124G>A		intron	N/A	NP_001307681.2
	STS	NM_001320750.3		c.33-19124G>A		intron	N/A	NP_001307679.1
	STS	NM_001320751.2		c.33-19124G>A		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.-4-19124G>A		intron	N/A	ENSP00000501534.1
	STS	ENST00000217961.5	TSL:1	c.-5+14386G>A		intron	N/A	ENSP00000217961.5
	STS	ENST00000666110.2		c.-4-19124G>A		intron	N/A	ENSP00000499472.2

Frequencies

GnomAD3 genomes AF: 0.234 AC: 25995 AN: 111007 Hom.: 2523 Cov.: 23

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0767

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.132

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.234 AC: 26002 AN: 111060 Hom.: 2521 Cov.: 23 AF XY: 0.238 AC XY: 7922 AN XY: 33344

African (AFR) AF: 0.101 AC: 3097 AN: 30673

American (AMR) AF: 0.408 AC: 4248 AN: 10412

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 632 AN: 2632

East Asian (EAS) AF: 0.305 AC: 1070 AN: 3503

South Asian (SAS) AF: 0.369 AC: 957 AN: 2594

European-Finnish (FIN) AF: 0.268 AC: 1587 AN: 5928

Middle Eastern (MID) AF: 0.126 AC: 27 AN: 214

European-Non Finnish (NFE) AF: 0.264 AC: 13971 AN: 52908

Other (OTH) AF: 0.238 AC: 361 AN: 1518

Alfa AF: 0.251 Hom.: 12729

Bravo AF: 0.240

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.89
DANN	Benign	0.17
PhyloP100		-0.55
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: rs1000900; hg19: chrX-7152113;