Variant chrX-7253206-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001320752.2(STS):c.7A>T(p.Ile3Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 1,209,220 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 80 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.00014 ( 0 hom. 78 hem. )

Consequence

STS
NM_001320752.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.143

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005499363).

BP6

Variant X-7253206-A-T is Benign according to our data. Variant chrX-7253206-A-T is described in ClinVar as [Benign]. Clinvar id is 2659916.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STS	NM_001320752.2 linkuse as main transcript	c.7A>T	p.Ile3Phe	missense_variant	3/11	ENST00000674429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STS	ENST00000674429.1 linkuse as main transcript	c.7A>T	p.Ile3Phe	missense_variant	3/11		NM_001320752.2	P1

Frequencies

GnomAD3 genomes

AF:

0.0000539

AC:

AN:

111415

Hom.:

Cov.:

AF XY:

0.0000595

AC XY:

AN XY:

33609

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00231

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000246

AC:

AN:

182852

Hom.:

AF XY:

0.000238

AC XY:

AN XY:

67354

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00226

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000142

AC:

156

AN:

1097753

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

363153

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00259

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000356

Gnomad4 OTH exome

AF:

0.000239

GnomAD4 genome

AF:

0.0000538

AC:

AN:

111467

Hom.:

Cov.:

AF XY:

0.0000594

AC XY:

AN XY:

33671

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00232

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.000239

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

STS: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.38

CADD

Benign

0.24

DANN

Benign

0.43

DEOGEN2

Uncertain

0.44

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.42

M_CAP

Benign

0.017

MetaRNN

Benign

0.0055

MetaSVM

Uncertain

-0.16

MutationAssessor

Benign

0.060

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.0

REVEL

Benign

0.22

Sift

Benign

0.10

Sift4G

Benign

0.21

Polyphen

0.0010

Vest4

0.040

MutPred

0.51

Gain of loop (P = 0.0045);

MVP

0.23

MPC

0.57

ClinPred

0.0090

GERP RS

-3.6

Varity_R

0.094

gMVP

0.56

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over