rs137853169

Positions:

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The NM_001320752.2(STS):​c.1316A>G​(p.His439Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 23)

Consequence

STS
NM_001320752.2 missense

Scores

10
6
1

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.50
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.968
PP5
Variant X-7334060-A-G is Pathogenic according to our data. Variant chrX-7334060-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 10556.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-7334060-A-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
STSNM_001320752.2 linkuse as main transcriptc.1316A>G p.His439Arg missense_variant 10/11 ENST00000674429.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
STSENST00000674429.1 linkuse as main transcriptc.1316A>G p.His439Arg missense_variant 10/11 NM_001320752.2 P1

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
23

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

X-linked ichthyosis with steryl-sulfatase deficiency Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMAug 15, 1997- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.91
BayesDel_addAF
Pathogenic
0.59
D
BayesDel_noAF
Pathogenic
0.61
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.89
D
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Pathogenic
0.97
D
M_CAP
Uncertain
0.16
D
MetaRNN
Pathogenic
0.97
D
MetaSVM
Pathogenic
0.96
D
MutationAssessor
Pathogenic
3.5
M
MutationTaster
Benign
1.0
A
PrimateAI
Uncertain
0.60
T
PROVEAN
Pathogenic
-7.6
D
REVEL
Pathogenic
0.91
Sift
Uncertain
0.0040
D
Sift4G
Uncertain
0.0060
D
Polyphen
1.0
D
Vest4
0.82
MutPred
0.86
Loss of helix (P = 0.079);
MVP
1.0
MPC
1.1
ClinPred
1.0
D
GERP RS
4.0
Varity_R
0.98
gMVP
0.96

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.

Other links and lift over

dbSNP: rs137853169; hg19: chrX-7252101; API