X-7253206-A-G

Variant names:

• chrX-7253206-A-G
• rs753519141
• NM_001320752.2:c.7A>G

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.7A>G​(p.Ile3Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,753 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I3F) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: STS NM_001320752.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143
• 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, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet

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 (MetaRNN=0.053425997).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320752.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STS	NM_001320752.2	MANE Select	c.7A>G	p.Ile3Val	missense	Exon 3 of 11	NP_001307681.2	A0A590UJL0
	STS	NM_001320750.3		c.43A>G	p.Ile15Val	missense	Exon 3 of 11	NP_001307679.1
	STS	NM_001320751.2		c.43A>G	p.Ile15Val	missense	Exon 4 of 12	NP_001307680.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STS	ENST00000674429.1	MANE Select	c.7A>G	p.Ile3Val	missense	Exon 3 of 11	ENSP00000501534.1	A0A590UJL0
	STS	ENST00000217961.5	TSL:1	c.7A>G	p.Ile3Val	missense	Exon 2 of 10	ENSP00000217961.5	A0A590UJL0
	STS	ENST00000666110.2		c.7A>G	p.Ile3Val	missense	Exon 3 of 11	ENSP00000499472.2	A0A590UJL0

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097753 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363153

African (AFR) AF: 0.00 AC: 0 AN: 26391

American (AMR) AF: 0.00 AC: 0 AN: 35184

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19382

East Asian (EAS) AF: 0.00 AC: 0 AN: 30202

South Asian (SAS) AF: 0.00 AC: 0 AN: 54114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40519

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4113

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841778

Other (OTH) AF: 0.00 AC: 0 AN: 46070

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.050
DANN	Benign	0.36
DEOGEN2	Benign	0.35	T
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.053	T
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Benign	-0.055	N
PhyloP100		-0.14
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.096
Sift	Benign	0.28	T
Sift4G	Benign	0.42	T
Polyphen		0.0010	B
Vest4		0.072
MutPred		0.33		Loss of catalytic residue at L13 (P = 0.0245)
MVP		0.082
MPC		0.23
ClinPred		0.37	T
GERP RS		-3.6
Varity_R		0.031
gMVP		0.47
Mutation Taster		=96/4	polymorphism

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: rs753519141; hg19: chrX-7171247;