X-7148083-G-A

Variant names:

• chrX-7148083-G-A
• rs748017610
• NM_012080.5:c.31C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_012080.5(PUDP):​c.31C>T​(p.Leu11Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000127 in 1,024,309 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.000013 (0 hom. 9 hem.)
• Consequence: PUDP NM_012080.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.09
• Publications: 0 publications found

Genes affected

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]

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]

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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17783132).
• BS2: High Hemizygotes in GnomAdExome4 at 9 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012080.5. 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
	PUDP	NM_012080.5	MANE Select	c.31C>T	p.Leu11Phe	missense	Exon 1 of 4	NP_036212.3	Q08623-1
	STS	NM_001320752.2	MANE Select	c.-134G>A		splice_region	Exon 1 of 11	NP_001307681.2	A0A590UJL0
	STS	NM_001320752.2	MANE Select	c.-134G>A		5_prime_UTR	Exon 1 of 11	NP_001307681.2	A0A590UJL0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PUDP	ENST00000381077.10	TSL:1 MANE Select	c.31C>T	p.Leu11Phe	missense	Exon 1 of 4	ENSP00000370467.6	Q08623-1
	STS	ENST00000674429.1	MANE Select	c.-134G>A		splice_region	Exon 1 of 11	ENSP00000501534.1	A0A590UJL0
	STS	ENST00000674429.1	MANE Select	c.-134G>A		5_prime_UTR	Exon 1 of 11	ENSP00000501534.1	A0A590UJL0

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD2 exomes AF: 0.0000439 AC: 4 AN: 91106 AF XY: 0.000101

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000127 AC: 13 AN: 1024309 Hom.: 0 Cov.: 29 AF XY: 0.0000273 AC XY: 9 AN XY: 330097

African (AFR) AF: 0.00 AC: 0 AN: 22000

American (AMR) AF: 0.00 AC: 0 AN: 25242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17623

East Asian (EAS) AF: 0.00 AC: 0 AN: 23865

South Asian (SAS) AF: 0.000273 AC: 13 AN: 47570

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37110

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3974

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 804034

Other (OTH) AF: 0.00 AC: 0 AN: 42891

GnomAD4 genome Cov.: 22

ExAC AF: 0.0000506 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.075	T
FATHMM_MKL	Benign	0.31	N
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.1
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.094
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.022	D
Polyphen		0.10	B
Vest4		0.44
MutPred		0.58		Gain of glycosylation at T9 (P = 0.1443)
MVP		0.36
MPC		0.099
ClinPred		0.078	T
GERP RS		2.5
PromoterAI		-0.15	Neutral
Varity_R		0.60
gMVP		0.61
Mutation Taster		=53/47	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: rs748017610; hg19: chrX-7066124;