NM_001320752.2:c.250G>C

Variant names:

• chrX-7257354-G-C
• rs1555956244
• NM_001320752.2:c.250G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001320752.2(STS):​c.250G>C​(p.Val84Leu) 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 1,097,922 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. 13/21 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. V84I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: STS NM_001320752.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154
• 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: Orphanet, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, Genomics England PanelApp

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24986133).

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.250G>C	p.Val84Leu	missense	Exon 4 of 11	NP_001307681.2	A0A590UJL0
	STS	NM_001320750.3		c.286G>C	p.Val96Leu	missense	Exon 4 of 11	NP_001307679.1
	STS	NM_001320751.2		c.286G>C	p.Val96Leu	missense	Exon 5 of 12	NP_001307680.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STS	ENST00000674429.1	MANE Select	c.250G>C	p.Val84Leu	missense	Exon 4 of 11	ENSP00000501534.1	A0A590UJL0
	STS	ENST00000217961.5	TSL:1	c.250G>C	p.Val84Leu	missense	Exon 3 of 10	ENSP00000217961.5	A0A590UJL0
	STS	ENST00000666110.2		c.250G>C	p.Val84Leu	missense	Exon 4 of 11	ENSP00000499472.2	A0A590UJL0

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097922 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 363284

African (AFR) AF: 0.00 AC: 0 AN: 26398

American (AMR) AF: 0.00 AC: 0 AN: 35190

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19383

East Asian (EAS) AF: 0.00 AC: 0 AN: 30196

South Asian (SAS) AF: 0.00 AC: 0 AN: 54113

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40508

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4131

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841935

Other (OTH) AF: 0.00 AC: 0 AN: 46068

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	0.59
DANN	Benign	0.92
DEOGEN2	Uncertain	0.68	D
FATHMM_MKL	Benign	0.051	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.25	T
MetaSVM	Uncertain	0.069	D
MutationAssessor	Benign	1.5	L
PhyloP100		0.15
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.34
Sift	Benign	0.13	T
Sift4G	Benign	0.12	T
Polyphen		0.0030	B
Vest4		0.21
MutPred		0.66		Loss of sheet (P = 0.0457)
MVP		0.66
MPC		0.29
ClinPred		0.093	T
GERP RS		-4.6
Varity_R		0.18
gMVP		0.78
Mutation Taster		=94/6	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: rs1555956244; hg19: chrX-7175395;