Genetic Variant PUDP:p.Ala95Gly (chrX-7077446-G-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_012080.5(PUDP):c.284C>G(p.Ala95Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000918 in 1,089,527 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A95V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 9.2e-7 ( 0 hom. 1 hem. )

Consequence

PUDP
NM_012080.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.85

Publications

0 publications found

Variant links:

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]

PUDP links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.803

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PUDP	NM_012080.5	MANE Select	c.284C>G	p.Ala95Gly	missense	Exon 3 of 4	NP_036212.3	Q08623-1
PUDP	NM_001135565.2		c.353C>G	p.Ala118Gly	missense	Exon 4 of 5	NP_001129037.1	Q08623-4
PUDP	NM_001178135.2		c.284C>G	p.Ala95Gly	missense	Exon 3 of 4	NP_001171606.1	Q08623-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PUDP	ENST00000381077.10	TSL:1 MANE Select	c.284C>G	p.Ala95Gly	missense	Exon 3 of 4	ENSP00000370467.6	Q08623-1
PUDP	ENST00000424830.6	TSL:3	c.353C>G	p.Ala118Gly	missense	Exon 4 of 5	ENSP00000396452.2	Q08623-4
PUDP	ENST00000934726.1		c.284C>G	p.Ala95Gly	missense	Exon 3 of 4	ENSP00000604785.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.18e-7

AC:

AN:

1089527

Hom.:

Cov.:

AF XY:

0.00000281

AC XY:

AN XY:

355521

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26279

American (AMR)

AF:

0.00

AC:

AN:

35093

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19311

East Asian (EAS)

AF:

0.00

AC:

AN:

30147

South Asian (SAS)

AF:

0.00

AC:

AN:

53686

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40423

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4108

European-Non Finnish (NFE)

AF:

0.00000120

AC:

AN:

834699

Other (OTH)

AF:

0.00

AC:

AN:

45781

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.16

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.0049

MetaRNN

Pathogenic

0.80

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.2

PhyloP100

3.8

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.14

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.019

Polyphen

0.98

Vest4

0.38

MutPred

0.75

Gain of ubiquitination at K97 (P = 0.1306)

MVP

0.088

MPC

0.37

ClinPred

0.96

GERP RS

0.067

Varity_R

0.81

gMVP

0.81

Mutation Taster

=78/22

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over