Genetic Variant PUDP:p.Asp121Asn (chrX-7077369-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_012080.5(PUDP):c.361G>A(p.Asp121Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000637 in 1,208,720 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 26 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 0.00015 ( 0 hom., 5 hem., cov: 23)

Exomes 𝑓: 0.000055 ( 0 hom. 21 hem. )

Consequence

PUDP
NM_012080.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0460

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.036495417).

BS2

High Hemizygotes in GnomAd4 at 5 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PUDP	NM_012080.5	MANE Select	c.361G>A	p.Asp121Asn	missense	Exon 3 of 4	NP_036212.3	Q08623-1
PUDP	NM_001135565.2		c.430G>A	p.Asp144Asn	missense	Exon 4 of 5	NP_001129037.1	Q08623-4
PUDP	NM_001178135.2		c.361G>A	p.Asp121Asn	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.361G>A	p.Asp121Asn	missense	Exon 3 of 4	ENSP00000370467.6	Q08623-1
PUDP	ENST00000424830.6	TSL:3	c.430G>A	p.Asp144Asn	missense	Exon 4 of 5	ENSP00000396452.2	Q08623-4
PUDP	ENST00000934726.1		c.361G>A	p.Asp121Asn	missense	Exon 3 of 4	ENSP00000604785.1

Frequencies

GnomAD3 genomes

AF:

0.000153

AC:

AN:

111120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000197

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000192

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00172

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000565

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000122

AC:

AN:

180482

AF XY:

0.000105

show subpopulations

Gnomad AFR exome

AF:

0.000243

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000890

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000743

Gnomad OTH exome

AF:

0.000225

GnomAD4 exome

AF:

0.0000547

AC:

AN:

1097551

Hom.:

Cov.:

AF XY:

0.0000579

AC XY:

AN XY:

363003

show subpopulations

African (AFR)

AF:

0.000189

AC:

AN:

26399

American (AMR)

AF:

0.0000284

AC:

AN:

35165

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19380

East Asian (EAS)

AF:

0.000895

AC:

AN:

30181

South Asian (SAS)

AF:

0.0000185

AC:

AN:

54060

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40481

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4135

European-Non Finnish (NFE)

AF:

0.0000273

AC:

AN:

841696

Other (OTH)

AF:

0.0000651

AC:

AN:

46054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000153

AC:

AN:

111169

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

AN XY:

33375

show subpopulations

African (AFR)

AF:

0.000196

AC:

AN:

30594

American (AMR)

AF:

0.000191

AC:

AN:

10452

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2640

East Asian (EAS)

AF:

0.00172

AC:

AN:

3487

South Asian (SAS)

AF:

0.00

AC:

AN:

2592

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5968

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.0000566

AC:

AN:

53046

Other (OTH)

AF:

0.00

AC:

AN:

1492

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.000132

ESP6500AA

AF:

0.000284

AC:

ESP6500EA

AF:

0.000153

AC:

ExAC

AF:

0.0000827

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-1.0

CADD

Benign

8.4

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.043

FATHMM_MKL

Benign

0.095

LIST_S2

Benign

0.45

M_CAP

Benign

0.0027

MetaRNN

Benign

0.036

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.82

PhyloP100

0.046

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.7

REVEL

Benign

0.043

Sift

Benign

0.19

Sift4G

Benign

0.39

Polyphen

0.0030

Vest4

0.070

MVP

0.22

MPC

0.066

ClinPred

0.041

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.48

Mutation Taster

=97/3

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over