rs5978405

Variant names:

• chrX-7291386-T-A
• rs5978405
• NM_001320752.2:c.944-13660T>A

Your query was ambiguous. Multiple possible variants found:

• chrX-7291386-T-A
• chrX-7291386-T-C
• chrX-7291386-T-G

Variant summary

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

The NM_001320752.2(STS):​c.944-13660T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 110,640 control chromosomes in the GnomAD database, including 5,163 homozygotes. There are 11,268 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 (5163 hom., 11268 hem., cov: 23)
• Consequence: STS NM_001320752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150
• Publications: 1 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: Orphanet, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, Genomics England PanelApp

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 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.944-13660T>A		intron	N/A	NP_001307681.2	A0A590UJL0
	STS	NM_001320750.3		c.980-13660T>A		intron	N/A	NP_001307679.1
	STS	NM_001320751.2		c.980-13660T>A		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.944-13660T>A		intron	N/A	ENSP00000501534.1	A0A590UJL0
	STS	ENST00000217961.5	TSL:1	c.944-13660T>A		intron	N/A	ENSP00000217961.5	A0A590UJL0
	STS	ENST00000666110.2		c.944-13660T>A		intron	N/A	ENSP00000499472.2	A0A590UJL0

Frequencies

GnomAD3 genomes AF: 0.354 AC: 39157 AN: 110584 Hom.: 5163 Cov.: 23

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.374

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.354 AC: 39152 AN: 110640 Hom.: 5163 Cov.: 23 AF XY: 0.342 AC XY: 11268 AN XY: 32936

African (AFR) AF: 0.282 AC: 8592 AN: 30465

American (AMR) AF: 0.336 AC: 3496 AN: 10406

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 933 AN: 2627

East Asian (EAS) AF: 0.405 AC: 1402 AN: 3466

South Asian (SAS) AF: 0.222 AC: 584 AN: 2634

European-Finnish (FIN) AF: 0.379 AC: 2212 AN: 5839

Middle Eastern (MID) AF: 0.360 AC: 77 AN: 214

European-Non Finnish (NFE) AF: 0.395 AC: 20870 AN: 52814

Other (OTH) AF: 0.372 AC: 560 AN: 1507

Alfa AF: 0.198 Hom.: 961

Bravo AF: 0.356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.4
DANN	Benign	0.72
PhyloP100		0.015
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: rs5978405; hg19: chrX-7209427;