rs727519

Variant names:

• chrX-7214204-G-C
• rs727519
• NM_001320752.2:c.-5+23196G>C

Variant summary

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

The NM_001320752.2(STS):​c.-5+23196G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 111,777 control chromosomes in the GnomAD database, including 2,523 homozygotes. There are 8,188 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 (2523 hom., 8188 hem., cov: 23)
• Consequence: STS NM_001320752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.841
• 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: PanelApp Australia, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Orphanet

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 = 0.397 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.-5+23196G>C		intron	N/A	NP_001307681.2	A0A590UJL0
	STS	NM_001320750.3		c.32+23196G>C		intron	N/A	NP_001307679.1
	STS	NM_001320751.2		c.32+23196G>C		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.-5+23196G>C		intron	N/A	ENSP00000501534.1	A0A590UJL0
	STS	ENST00000666110.2		c.-5+23196G>C		intron	N/A	ENSP00000499472.2	A0A590UJL0
	STS	ENST00000870798.1		c.-4-38992G>C		intron	N/A	ENSP00000540857.1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 26246 AN: 111725 Hom.: 2525 Cov.: 23

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.0775

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.235 AC: 26253 AN: 111777 Hom.: 2523 Cov.: 23 AF XY: 0.241 AC XY: 8188 AN XY: 34019

African (AFR) AF: 0.102 AC: 3145 AN: 30903

American (AMR) AF: 0.408 AC: 4307 AN: 10566

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 635 AN: 2637

East Asian (EAS) AF: 0.306 AC: 1080 AN: 3527

South Asian (SAS) AF: 0.369 AC: 986 AN: 2670

European-Finnish (FIN) AF: 0.268 AC: 1617 AN: 6034

Middle Eastern (MID) AF: 0.137 AC: 29 AN: 212

European-Non Finnish (NFE) AF: 0.265 AC: 14037 AN: 53013

Other (OTH) AF: 0.238 AC: 364 AN: 1531

Alfa AF: 0.260 Hom.: 1660

Bravo AF: 0.239

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.49
PhyloP100		0.84

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs727519;

hg19: chrX-7132245;