ENST00000664306.2:n.*83+56895G>A

Variant names:

• chrX-7643222-G-A
• rs923644
• ENST00000664306.2:n.*83+56895G>A

Variant summary

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

The ENST00000664306.2(STS):​n.*83+56895G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0401 in 110,399 control chromosomes in the GnomAD database, including 180 homozygotes. There are 1,233 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 0.040 (180 hom., 1233 hem., cov: 22)
• Consequence: STS ENST00000664306.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74
• Publications: 0 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)

ENSG00000296839 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000664306.2. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STS	ENST00000664306.2		n.*83+56895G>A		intron	N/A	ENSP00000499549.2
	ENSG00000296839	ENST00000742933.1		n.503-35111G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0400 AC: 4412 AN: 110343 Hom.: 176 Cov.: 22

Gnomad AFR AF: 0.0676

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0368

Gnomad ASJ AF: 0.0534

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.0805

Gnomad FIN AF: 0.0121

Gnomad MID AF: 0.0678

Gnomad NFE AF: 0.0130

Gnomad OTH AF: 0.0474

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

GnomAD4 genome AF: 0.0401 AC: 4424 AN: 110399 Hom.: 180 Cov.: 22 AF XY: 0.0378 AC XY: 1233 AN XY: 32659

African (AFR) AF: 0.0675 AC: 2049 AN: 30359

American (AMR) AF: 0.0373 AC: 383 AN: 10264

Ashkenazi Jewish (ASJ) AF: 0.0534 AC: 140 AN: 2624

East Asian (EAS) AF: 0.228 AC: 788 AN: 3463

South Asian (SAS) AF: 0.0792 AC: 205 AN: 2588

European-Finnish (FIN) AF: 0.0121 AC: 71 AN: 5870

Middle Eastern (MID) AF: 0.0651 AC: 14 AN: 215

European-Non Finnish (NFE) AF: 0.0131 AC: 690 AN: 52835

Other (OTH) AF: 0.0561 AC: 84 AN: 1496

Alfa AF: 0.00873 Hom.: 35

Bravo AF: 0.0464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.8
DANN	Benign	0.60
PhyloP100		1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs923644; hg19: chrX-7561263;