X-7325263-G-T

Variant names:

• chrX-7325263-G-T
• rs4403552
• NM_001320752.2:c.1082-76G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001320752.2(STS):​c.1082-76G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000102 in 982,440 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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: not found (cov: 22)
  • Exomes 𝑓: 0.0000010 (0 hom. 0 hem.)
• Consequence: STS NM_001320752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.56
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STS	NM_001320752.2	c.1082-76G>T		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.1082-76G>T		intron_variant	Intron 8 of 10		NM_001320752.2	ENSP00000501534.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000102 AC: 1 AN: 982440 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 289232

African (AFR) AF: 0.00 AC: 0 AN: 24138

American (AMR) AF: 0.00 AC: 0 AN: 30980

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18384

East Asian (EAS) AF: 0.00 AC: 0 AN: 28682

South Asian (SAS) AF: 0.00 AC: 0 AN: 49717

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38838

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3903

European-Non Finnish (NFE) AF: 0.00000134 AC: 1 AN: 745579

Other (OTH) AF: 0.00 AC: 0 AN: 42219

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.0010
DANN	Benign	0.35
PhyloP100		-5.6

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: rs4403552; hg19: chrX-7243304;