rs1131289

Variant names:

• chrX-7352955-A-G
• rs1131289
• NM_001320752.2:c.*2694A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001320752.2(STS):​c.*2694A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.66 (16708 hom., 20406 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: STS NM_001320752.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116
• 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: PanelApp Australia, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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.*2694A>G		3_prime_UTR	Exon 11 of 11	NP_001307681.2	A0A590UJL0
	STS	NM_001320750.3		c.*2694A>G		3_prime_UTR	Exon 11 of 11	NP_001307679.1
	STS	NM_001320751.2		c.*2694A>G		3_prime_UTR	Exon 12 of 12	NP_001307680.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STS	ENST00000674429.1	MANE Select	c.*2694A>G		3_prime_UTR	Exon 11 of 11	ENSP00000501534.1	A0A590UJL0
	STS	ENST00000217961.5	TSL:1	c.*2694A>G		3_prime_UTR	Exon 10 of 10	ENSP00000217961.5	A0A590UJL0
	STS	ENST00000666110.2		c.*2694A>G		3_prime_UTR	Exon 11 of 11	ENSP00000499472.2	A0A590UJL0

Frequencies

GnomAD3 genomes AF: 0.655 AC: 70875 AN: 108158 Hom.: 16714 Cov.: 22

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.921

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.833

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.670

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.655 AC: 70877 AN: 108203 Hom.: 16708 Cov.: 22 AF XY: 0.659 AC XY: 20406 AN XY: 30987

African (AFR) AF: 0.565 AC: 16501 AN: 29223

American (AMR) AF: 0.532 AC: 5330 AN: 10024

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 1967 AN: 2624

East Asian (EAS) AF: 0.656 AC: 2284 AN: 3481

South Asian (SAS) AF: 0.604 AC: 1535 AN: 2542

European-Finnish (FIN) AF: 0.710 AC: 3959 AN: 5576

Middle Eastern (MID) AF: 0.840 AC: 179 AN: 213

European-Non Finnish (NFE) AF: 0.716 AC: 37498 AN: 52361

Other (OTH) AF: 0.674 AC: 995 AN: 1476

Alfa AF: 0.625 Hom.: 13618

Bravo AF: 0.632

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.28
DANN	Benign	0.57
PhyloP100		0.12
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

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

Other links and lift over

dbSNP: rs1131289;

hg19: chrX-7270996;