rs1473666

chrX-7148010-A-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001320752.2(STS):c.-207A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.68 (18532 hom., 21106 hem., cov: 21)
  • Exomes 𝑓: 0.61 (124680 hom. 180816 hem.)
  • Failed GnomAD Quality Control
• Consequence: STS NM_001320752.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340

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]

PUDP (HGNC:16818): (pseudouridine 5'-phosphatase) This gene encodes a member of the haloacid dehalogenase-like (HAD) hydrolase superfamily. The encoded protein has no known biological function. This gene has a pseudogene on chromosome 1. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BS2: High Homozygotes in GnomAd at 18530 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STS	NM_001320752.2	c.-207A>C		5_prime_UTR_variant	1/11	ENST00000674429.1
PUDP	NM_012080.5	c.61+43T>G		intron_variant		ENST00000381077.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STS	ENST00000674429.1	c.-207A>C		5_prime_UTR_variant	1/11		NM_001320752.2	P1
PUDP	ENST00000381077.10	c.61+43T>G		intron_variant		1	NM_012080.5	P1

Frequencies

GnomAD3 genomes AF: 0.677 AC: 73652 AN: 108741 Hom.: 18530 Cov.: 21 AF XY: 0.671 AC XY: 21053 AN XY: 31359

Gnomad AFR AF: 0.868

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.632

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.654

GnomAD3 exomes AF: 0.624 AC: 54692 AN: 87580 Hom.: 11594 AF XY: 0.635 AC XY: 18206 AN XY: 28688

Gnomad AFR exome AF: 0.878

Gnomad AMR exome AF: 0.636

Gnomad ASJ exome AF: 0.626

Gnomad EAS exome AF: 0.559

Gnomad SAS exome AF: 0.761

Gnomad FIN exome AF: 0.548

Gnomad NFE exome AF: 0.583

Gnomad OTH exome AF: 0.628

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.609 AC: 588589 AN: 966760 Hom.: 124680 Cov.: 17 AF XY: 0.622 AC XY: 180816 AN XY: 290862

Gnomad4 AFR exome AF: 0.878

Gnomad4 AMR exome AF: 0.643

Gnomad4 ASJ exome AF: 0.634

Gnomad4 EAS exome AF: 0.645

Gnomad4 SAS exome AF: 0.758

Gnomad4 FIN exome AF: 0.546

Gnomad4 NFE exome AF: 0.592

Gnomad4 OTH exome AF: 0.617

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.678 AC: 73702 AN: 108781 Hom.: 18532 Cov.: 21 AF XY: 0.672 AC XY: 21106 AN XY: 31409

Gnomad4 AFR AF: 0.868

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.634

Gnomad4 EAS AF: 0.592

Gnomad4 SAS AF: 0.754

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.592

Gnomad4 OTH AF: 0.650

Alfa AF: 0.637 Hom.: 14679

Bravo AF: 0.690

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	9.0
Dann	Benign	0.30

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: rs1473666; hg19: chrX-7066051; COSMIC: COSV66903752; COSMIC: COSV66903752;