X-7105818-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012080.5(PUDP):​c.82G>T​(p.Val28Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: PUDP NM_012080.5 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10839462).

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>T	p.Val28Leu	missense	Exon 2 of 4	NP_036212.3	Q08623-1
	PUDP	NM_001135565.2		c.151G>T	p.Val51Leu	missense	Exon 3 of 5	NP_001129037.1	Q08623-4
	PUDP	NM_001178135.2		c.82G>T	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>T	p.Val28Leu	missense	Exon 2 of 4	ENSP00000370467.6	Q08623-1
	PUDP	ENST00000424830.6	TSL:3	c.151G>T	p.Val51Leu	missense	Exon 3 of 5	ENSP00000396452.2	Q08623-4
	PUDP	ENST00000934726.1		c.82G>T	p.Val28Leu	missense	Exon 2 of 4	ENSP00000604785.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.4
DANN	Benign	0.86
DEOGEN2	Benign	0.038	T
FATHMM_MKL	Benign	0.18	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.11	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		0.055	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; COSMIC: COSV105929953;