X-7105818-C-G

Variant names:

• chrX-7105818-C-G
• rs753120243
• NM_012080.5:c.82G>C

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.82G>C​(p.Val28Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000142 in 1,195,738 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 3 hem., cov: 23)
  • Exomes 𝑓: 0.000013 (0 hom. 5 hem.)
• Consequence: PUDP NM_012080.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0960
• 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]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07276496).
• BS2: High Hemizygotes in GnomAd4 at 3 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.82G>C	p.Val28Leu	missense	Exon 2 of 4	NP_036212.3	Q08623-1
	PUDP	NM_001135565.2		c.151G>C	p.Val51Leu	missense	Exon 3 of 5	NP_001129037.1	Q08623-4
	PUDP	NM_001178135.2		c.82G>C	p.Val28Leu	missense	Exon 2 of 4	NP_001171606.1	Q08623-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PUDP	ENST00000381077.10	TSL:1 MANE Select	c.82G>C	p.Val28Leu	missense	Exon 2 of 4	ENSP00000370467.6	Q08623-1
	PUDP	ENST00000424830.6	TSL:3	c.151G>C	p.Val51Leu	missense	Exon 3 of 5	ENSP00000396452.2	Q08623-4
	PUDP	ENST00000934726.1		c.82G>C	p.Val28Leu	missense	Exon 2 of 4	ENSP00000604785.1

Frequencies

GnomAD3 genomes AF: 0.0000269 AC: 3 AN: 111366 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000561

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000664

GnomAD2 exomes AF: 0.0000345 AC: 6 AN: 174033 AF XY: 0.0000331

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000458

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000129 AC: 14 AN: 1084372 Hom.: 0 Cov.: 29 AF XY: 0.0000143 AC XY: 5 AN XY: 350290

African (AFR) AF: 0.00 AC: 0 AN: 26098

American (AMR) AF: 0.00 AC: 0 AN: 34690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19216

East Asian (EAS) AF: 0.000465 AC: 14 AN: 30139

South Asian (SAS) AF: 0.00 AC: 0 AN: 52756

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40423

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4081

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 831337

Other (OTH) AF: 0.00 AC: 0 AN: 45632

GnomAD4 genome AF: 0.0000269 AC: 3 AN: 111366 Hom.: 0 Cov.: 23 AF XY: 0.0000894 AC XY: 3 AN XY: 33560

African (AFR) AF: 0.00 AC: 0 AN: 30598

American (AMR) AF: 0.00 AC: 0 AN: 10481

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2643

East Asian (EAS) AF: 0.000561 AC: 2 AN: 3568

South Asian (SAS) AF: 0.00 AC: 0 AN: 2601

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5962

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53088

Other (OTH) AF: 0.000664 AC: 1 AN: 1506

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000414 AC: 5

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	Benign	0.18
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.2
DANN	Benign	0.88
DEOGEN2	Benign	0.038	T
FATHMM_MKL	Benign	0.18	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.91	L
PhyloP100		0.096
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.034
Sift	Benign	0.29	T
Sift4G	Benign	0.24	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.49		Gain of catalytic residue at V28 (P = 0.1351)
MVP		0.41
MPC		0.066
ClinPred		0.020	T
GERP RS		3.1
Varity_R		0.42
gMVP		0.50
Mutation Taster		=95/5	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: rs753120243; hg19: chrX-7023859;