rs2270112

Variant names:

• chrX-7252884-C-G
• rs2270112
• NM_001320752.2:c.-4-312C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-7252884-C-G
• chrX-7252884-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001320752.2(STS):​c.-4-312C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.69 (18761 hom., 22524 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: STS NM_001320752.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.07
• Publications: 5 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant X-7252884-C-G is Benign according to our data. Variant chrX-7252884-C-G is described in ClinVar as Benign. ClinVar VariationId is 1265834.Status of the report is criteria_provided_single_submitter, 1 stars.

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.-4-312C>G		intron	N/A	NP_001307681.2	A0A590UJL0
	STS	NM_001320750.3		c.33-312C>G		intron	N/A	NP_001307679.1
	STS	NM_001320751.2		c.33-312C>G		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.-4-312C>G		intron	N/A	ENSP00000501534.1	A0A590UJL0
	STS	ENST00000217961.5	TSL:1	c.-4-312C>G		intron	N/A	ENSP00000217961.5	A0A590UJL0
	STS	ENST00000666110.2		c.-4-312C>G		intron	N/A	ENSP00000499472.2	A0A590UJL0

Frequencies

GnomAD3 genomes AF: 0.691 AC: 76217 AN: 110250 Hom.: 18759 Cov.: 22

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.722

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.552

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.688

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.691 AC: 76263 AN: 110308 Hom.: 18761 Cov.: 22 AF XY: 0.692 AC XY: 22524 AN XY: 32544

African (AFR) AF: 0.689 AC: 20865 AN: 30266

American (AMR) AF: 0.805 AC: 8326 AN: 10349

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 1596 AN: 2635

East Asian (EAS) AF: 0.715 AC: 2480 AN: 3469

South Asian (SAS) AF: 0.610 AC: 1587 AN: 2600

European-Finnish (FIN) AF: 0.665 AC: 3871 AN: 5818

Middle Eastern (MID) AF: 0.536 AC: 113 AN: 211

European-Non Finnish (NFE) AF: 0.680 AC: 35912 AN: 52795

Other (OTH) AF: 0.689 AC: 1030 AN: 1496

Alfa AF: 0.468 Hom.: 1823

Bravo AF: 0.705

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.19
DANN	Benign	0.32
PhyloP100		-2.1
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: rs2270112;

hg19: chrX-7170925;