NM_001320752.2:c.-4-1719T>C

Variant names:

• chrX-7251477-T-C
• rs5934769
• NM_001320752.2:c.-4-1719T>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.-4-1719T>C 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 108,724 control chromosomes in the GnomAD database, including 5,127 homozygotes. There are 10,699 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 (5127 hom., 10699 hem., cov: 21)
• Consequence: STS NM_001320752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92
• 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)

ENSG00000293893 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STS	NM_001320752.2	c.-4-1719T>C		intron_variant	Intron 2 of 10	ENST00000674429.1	NP_001307681.2
STS	NM_001320750.3	c.33-1719T>C		intron_variant	Intron 2 of 10		NP_001307679.1
STS	NM_001320751.2	c.33-1719T>C		intron_variant	Intron 3 of 11		NP_001307680.1
STS	NM_000351.7	c.-4-1719T>C		intron_variant	Intron 1 of 9		NP_000342.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STS	ENST00000674429.1	c.-4-1719T>C		intron_variant	Intron 2 of 10		NM_001320752.2	ENSP00000501534.1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 38528 AN: 108675 Hom.: 5127 Cov.: 21

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.381

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.354 AC: 38519 AN: 108724 Hom.: 5127 Cov.: 21 AF XY: 0.343 AC XY: 10699 AN XY: 31172

African (AFR) AF: 0.283 AC: 8450 AN: 29859

American (AMR) AF: 0.334 AC: 3381 AN: 10126

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 926 AN: 2610

East Asian (EAS) AF: 0.401 AC: 1338 AN: 3338

South Asian (SAS) AF: 0.225 AC: 556 AN: 2475

European-Finnish (FIN) AF: 0.381 AC: 2130 AN: 5591

Middle Eastern (MID) AF: 0.362 AC: 75 AN: 207

European-Non Finnish (NFE) AF: 0.395 AC: 20684 AN: 52369

Other (OTH) AF: 0.377 AC: 560 AN: 1486

Alfa AF: 0.366 Hom.: 4271

Bravo AF: 0.356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.37
DANN	Benign	0.48
PhyloP100		-1.9
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: rs5934769; hg19: chrX-7169518;