X-7323041-C-G

Variant names:

• chrX-7323041-C-G
• rs5934937
• NM_001320752.2:c.1082-2298C>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.1082-2298C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 110,655 control chromosomes in the GnomAD database, including 4,433 homozygotes. There are 10,001 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 0.31 (4433 hom., 10001 hem., cov: 23)
• Consequence: STS NM_001320752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.559
• 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: 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 (EAS) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STS	NM_001320752.2	c.1082-2298C>G		intron_variant	Intron 8 of 10	ENST00000674429.1	NP_001307681.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STS	ENST00000674429.1	c.1082-2298C>G		intron_variant	Intron 8 of 10		NM_001320752.2	ENSP00000501534.1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 34624 AN: 110600 Hom.: 4432 Cov.: 23

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.349

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.313 AC: 34614 AN: 110655 Hom.: 4433 Cov.: 23 AF XY: 0.304 AC XY: 10001 AN XY: 32909

African (AFR) AF: 0.148 AC: 4516 AN: 30529

American (AMR) AF: 0.312 AC: 3249 AN: 10403

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 933 AN: 2639

East Asian (EAS) AF: 0.404 AC: 1406 AN: 3482

South Asian (SAS) AF: 0.217 AC: 571 AN: 2634

European-Finnish (FIN) AF: 0.375 AC: 2171 AN: 5790

Middle Eastern (MID) AF: 0.335 AC: 71 AN: 212

European-Non Finnish (NFE) AF: 0.393 AC: 20760 AN: 52782

Other (OTH) AF: 0.337 AC: 510 AN: 1514

Alfa AF: 0.169 Hom.: 819

Bravo AF: 0.309

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.91
DANN	Benign	0.72
PhyloP100		-0.56
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: rs5934937; hg19: chrX-7241082;