chrX-7148010-A-G

Variant names:

• chrX-7148010-A-G
• rs1473666
• NM_001320752.2:c.-207A>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.-207A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000103 in 968,363 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0000010 (0 hom. 0 hem.)
• Consequence: STS NM_001320752.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340
• 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]

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]

MIR4767 (HGNC:41548): (microRNA 4767) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

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 (BayesDel_noAF=-0.92).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STS	NM_001320752.2	MANE Select	c.-207A>G		5_prime_UTR	Exon 1 of 11	NP_001307681.2
	PUDP	NM_012080.5	MANE Select	c.61+43T>C		intron	N/A	NP_036212.3
	STS	NM_001320751.2		c.-325A>G		5_prime_UTR	Exon 1 of 12	NP_001307680.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STS	ENST00000674429.1	MANE Select	c.-207A>G		5_prime_UTR	Exon 1 of 11	ENSP00000501534.1
	PUDP	ENST00000381077.10	TSL:1 MANE Select	c.61+43T>C		intron	N/A	ENSP00000370467.6
	STS	ENST00000658154.1		n.34A>G		non_coding_transcript_exon	Exon 1 of 12

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 0.00000103 AC: 1 AN: 968363 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 290981

African (AFR) AF: 0.00 AC: 0 AN: 20799

American (AMR) AF: 0.00 AC: 0 AN: 24856

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17152

East Asian (EAS) AF: 0.00 AC: 0 AN: 23096

South Asian (SAS) AF: 0.00 AC: 0 AN: 46469

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36879

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3824

European-Non Finnish (NFE) AF: 0.00000133 AC: 1 AN: 754379

Other (OTH) AF: 0.00 AC: 0 AN: 40909

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	8.3
DANN	Benign	0.57
PhyloP100		0.034
PromoterAI		0.024	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1473666; hg19: chrX-7066051;