chrX-7239611-G-A

Position:

• chrX-7239611-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001320752.2(STS):​c.-4-13585G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 110,531 control chromosomes in the GnomAD database, including 7,370 homozygotes. There are 13,594 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 0.43 (7370 hom., 13594 hem., cov: 23)
• Consequence: STS NM_001320752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STS	NM_001320752.2	c.-4-13585G>A		intron_variant		ENST00000674429.1	NP_001307681.2
STS	NM_000351.7	c.-4-13585G>A		intron_variant			NP_000342.3
STS	NM_001320750.3	c.33-13585G>A		intron_variant			NP_001307679.1
STS	NM_001320751.2	c.33-13585G>A		intron_variant			NP_001307680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STS	ENST00000674429.1	c.-4-13585G>A		intron_variant			NM_001320752.2	ENSP00000501534	P1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 46955 AN: 110478 Hom.: 7371 Cov.: 23 AF XY: 0.414 AC XY: 13572 AN XY: 32772

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.391

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.425 AC: 46976 AN: 110531 Hom.: 7370 Cov.: 23 AF XY: 0.414 AC XY: 13594 AN XY: 32835

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.360

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.427

Alfa AF: 0.257 Hom.: 1565

Bravo AF: 0.434

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.23
DANN	Benign	0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs5934740; hg19: chrX-7157652;