NM_001320752.2:c.52G>A

Variant names:

• chrX-7253251-G-A
• rs377179856
• NM_001320752.2:c.52G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001320752.2(STS):​c.52G>A​(p.Ala18Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000653 in 1,209,400 control chromosomes in the GnomAD database, including 1 homozygotes. There are 22 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000090 (0 hom., 2 hem., cov: 23)
  • Exomes 𝑓: 0.000063 (1 hom. 20 hem.)
• Consequence: STS NM_001320752.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0480

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0116457045).
• BP6: Variant X-7253251-G-A is Benign according to our data. Variant chrX-7253251-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 779550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000896 (10/111588) while in subpopulation EAS AF= 0.0017 (6/3532). AF 95% confidence interval is 0.000739. There are 0 homozygotes in gnomad4. There are 2 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STS	NM_001320752.2	c.52G>A	p.Ala18Thr	missense_variant	Exon 3 of 11	ENST00000674429.1	NP_001307681.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STS	ENST00000674429.1	c.52G>A	p.Ala18Thr	missense_variant	Exon 3 of 11		NM_001320752.2	ENSP00000501534.1

Frequencies

GnomAD3 genomes AF: 0.0000897 AC: 10 AN: 111534 Hom.: 0 Cov.: 23 AF XY: 0.0000593 AC XY: 2 AN XY: 33738

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00169

Gnomad SAS AF: 0.000382

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000376

Gnomad OTH AF: 0.000670

GnomAD3 exomes AF: 0.000104 AC: 19 AN: 183329 Hom.: 0 AF XY: 0.000148 AC XY: 10 AN XY: 67787

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000866

Gnomad SAS exome AF: 0.0000524

Gnomad FIN exome AF: 0.000125

Gnomad NFE exome AF: 0.0000367

Gnomad OTH exome AF: 0.000221

GnomAD4 exome AF: 0.0000629 AC: 69 AN: 1097812 Hom.: 1 Cov.: 31 AF XY: 0.0000551 AC XY: 20 AN XY: 363170

Gnomad4 AFR exome AF: 0.0000379

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000530

Gnomad4 SAS exome AF: 0.0000185

Gnomad4 FIN exome AF: 0.0000740

Gnomad4 NFE exome AF: 0.0000380

Gnomad4 OTH exome AF: 0.000347

GnomAD4 genome AF: 0.0000896 AC: 10 AN: 111588 Hom.: 0 Cov.: 23 AF XY: 0.0000592 AC XY: 2 AN XY: 33802

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00170

Gnomad4 SAS AF: 0.000383

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000376

Gnomad4 OTH AF: 0.000662

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000604

ExAC AF: 0.0000906 AC: 11

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

STS: BS2 -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

STS-related disorder Benign:1

Mar 08, 2021

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.29
DANN	Benign	0.74
DEOGEN2	Benign	0.37	T
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.14	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	1.1	L
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.18
Sift	Benign	0.57	T
Sift4G	Benign	0.56	T
Polyphen		0.023	B
Vest4		0.060
MVP		0.26
MPC		0.26
ClinPred		0.030	T
GERP RS		-2.8
Varity_R		0.067
gMVP		0.47

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

Other links and lift over

dbSNP: rs377179856; hg19: chrX-7171292;