chrX-7256772-G-A

Variant names:

• chrX-7256772-G-A
• rs17335568
• NM_001320752.2:c.138-470G>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.138-470G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 110,253 control chromosomes in the GnomAD database, including 5,138 homozygotes. There are 11,018 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 0.35 (5138 hom., 11018 hem., cov: 22)
• Consequence: STS NM_001320752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370
• 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STS	NM_001320752.2	c.138-470G>A		intron_variant	Intron 3 of 10	ENST00000674429.1	NP_001307681.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STS	ENST00000674429.1	c.138-470G>A		intron_variant	Intron 3 of 10		NM_001320752.2	ENSP00000501534.1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 38880 AN: 110201 Hom.: 5138 Cov.: 22

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.353 AC: 38873 AN: 110253 Hom.: 5138 Cov.: 22 AF XY: 0.339 AC XY: 11018 AN XY: 32545

African (AFR) AF: 0.282 AC: 8534 AN: 30316

American (AMR) AF: 0.335 AC: 3484 AN: 10397

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 937 AN: 2633

East Asian (EAS) AF: 0.394 AC: 1369 AN: 3473

South Asian (SAS) AF: 0.218 AC: 570 AN: 2617

European-Finnish (FIN) AF: 0.373 AC: 2153 AN: 5772

Middle Eastern (MID) AF: 0.352 AC: 76 AN: 216

European-Non Finnish (NFE) AF: 0.394 AC: 20774 AN: 52673

Other (OTH) AF: 0.369 AC: 549 AN: 1488

Alfa AF: 0.359 Hom.: 3563

Bravo AF: 0.356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.44
PhyloP100		-0.037
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: rs17335568; hg19: chrX-7174813;