NM_001320752.2:c.-5+14036C>G

Variant names:

• chrX-7205044-C-G
• rs5934671
• NM_001320752.2:c.-5+14036C>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.-5+14036C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 111,049 control chromosomes in the GnomAD database, including 3,333 homozygotes. There are 8,599 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 0.28 (3333 hom., 8599 hem., cov: 22)
• Consequence: STS NM_001320752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.327 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STS	NM_001320752.2	MANE Select	c.-5+14036C>G		intron	N/A	NP_001307681.2
	STS	NM_001320750.3		c.32+14036C>G		intron	N/A	NP_001307679.1
	STS	NM_001320751.2		c.32+14036C>G		intron	N/A	NP_001307680.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STS	ENST00000674429.1	MANE Select	c.-5+14036C>G		intron	N/A	ENSP00000501534.1
	STS	ENST00000666110.2		c.-5+14036C>G		intron	N/A	ENSP00000499472.2
	STS	ENST00000660000.2		c.-5+14036C>G		intron	N/A	ENSP00000499642.2

Frequencies

GnomAD3 genomes AF: 0.277 AC: 30786 AN: 110996 Hom.: 3339 Cov.: 22

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.0735

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.277 AC: 30768 AN: 111049 Hom.: 3333 Cov.: 22 AF XY: 0.258 AC XY: 8599 AN XY: 33311

African (AFR) AF: 0.249 AC: 7609 AN: 30531

American (AMR) AF: 0.191 AC: 2003 AN: 10486

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 801 AN: 2638

East Asian (EAS) AF: 0.129 AC: 453 AN: 3512

South Asian (SAS) AF: 0.0733 AC: 198 AN: 2700

European-Finnish (FIN) AF: 0.233 AC: 1380 AN: 5923

Middle Eastern (MID) AF: 0.303 AC: 64 AN: 211

European-Non Finnish (NFE) AF: 0.331 AC: 17501 AN: 52883

Other (OTH) AF: 0.290 AC: 435 AN: 1501

Alfa AF: 0.280 Hom.: 1763

Bravo AF: 0.275

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.73
DANN	Benign	0.52
PhyloP100		-0.28

Splicing

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

Other links and lift over

dbSNP: rs5934671; hg19: chrX-7123085;