X-7219197-C-T

Position:

• chrX-7219197-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001320752.2(STS):​c.-5+28189C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0241 in 112,039 control chromosomes in the GnomAD database, including 51 homozygotes. There are 701 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.024 (51 hom., 701 hem., cov: 23)
• Consequence: STS NM_001320752.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.912

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant X-7219197-C-T is Benign according to our data. Variant chrX-7219197-C-T is described in ClinVar as [Benign]. Clinvar id is 1265441.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STS	NM_001320752.2	c.-5+28189C>T		intron_variant		ENST00000674429.1	NP_001307681.2
STS	NM_001320750.3	c.32+28189C>T		intron_variant			NP_001307679.1
STS	NM_001320751.2	c.32+28189C>T		intron_variant			NP_001307680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STS	ENST00000674429.1	c.-5+28189C>T		intron_variant			NM_001320752.2	ENSP00000501534	P1

Frequencies

GnomAD3 genomes AF: 0.0241 AC: 2695 AN: 111985 Hom.: 51 Cov.: 23 AF XY: 0.0206 AC XY: 703 AN XY: 34167

Gnomad AFR AF: 0.0527

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.00341

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00521

Gnomad FIN AF: 0.00344

Gnomad MID AF: 0.0126

Gnomad NFE AF: 0.0164

Gnomad OTH AF: 0.0165

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

GnomAD4 genome AF: 0.0241 AC: 2696 AN: 112039 Hom.: 51 Cov.: 23 AF XY: 0.0205 AC XY: 701 AN XY: 34231

Gnomad4 AFR AF: 0.0527

Gnomad4 AMR AF: 0.0122

Gnomad4 ASJ AF: 0.00341

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00486

Gnomad4 FIN AF: 0.00344

Gnomad4 NFE AF: 0.0164

Gnomad4 OTH AF: 0.0163

Alfa AF: 0.0207 Hom.: 91

Bravo AF: 0.0265

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 26, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.26

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs142448158; hg19: chrX-7137238;