NM_001320752.2:c.219C>G

Variant names:

• chrX-7257323-C-G
• NM_001320752.2:c.219C>G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001320752.2(STS):​c.219C>G​(p.Ser73Arg) variant causes a missense change involving the alteration of a non-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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: STS NM_001320752.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.17
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.972

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.219C>G	p.Ser73Arg	missense	Exon 4 of 11	NP_001307681.2	A0A590UJL0
	STS	NM_001320750.3		c.255C>G	p.Ser85Arg	missense	Exon 4 of 11	NP_001307679.1
	STS	NM_001320751.2		c.255C>G	p.Ser85Arg	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.219C>G	p.Ser73Arg	missense	Exon 4 of 11	ENSP00000501534.1	A0A590UJL0
	STS	ENST00000217961.5	TSL:1	c.219C>G	p.Ser73Arg	missense	Exon 3 of 10	ENSP00000217961.5	A0A590UJL0
	STS	ENST00000666110.2		c.219C>G	p.Ser73Arg	missense	Exon 4 of 11	ENSP00000499472.2	A0A590UJL0

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 24

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.60	D
BayesDel_noAF	Pathogenic	0.62
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.95	D
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Pathogenic	0.74	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Pathogenic	0.93	D
MutationAssessor	Pathogenic	4.6	H
PhyloP100		1.2
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Pathogenic	0.81
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.86
MutPred		0.81		Gain of methylation at S78 (P = 0.0186)
MVP		0.99
MPC		0.96
ClinPred		1.0	D
GERP RS		1.4
Varity_R		0.98
gMVP		1.0
Mutation Taster		=48/52	disease causing

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

hg19: chrX-7175364;