Variant X-7077369-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 13/20 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

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:

PUDP (HGNC:):

PUDP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

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

BS2

High Hemizygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PUDP	NM_012080.5 linkuse as main transcript	c.361G>A	p.Asp121Asn	missense_variant	3/4	ENST00000381077.10	NP_036212.3	Q08623-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PUDP	ENST00000381077.10 linkuse as main transcript	c.361G>A	p.Asp121Asn	missense_variant	3/4	1	NM_012080.5	ENSP00000370467.6		Q08623-1

Frequencies

GnomAD3 genomes

AF:

0.000153

AC:

AN:

111120

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

AN XY:

33316

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

GnomAD3 exomes

AF:

0.000122

AC:

AN:

180482

Hom.:

AF XY:

0.000105

AC XY:

AN XY:

66558

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 SAS exome

AF:

0.00

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

Gnomad4 AFR exome

AF:

0.000189

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000895

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000273

Gnomad4 OTH exome

AF:

0.0000651

GnomAD4 genome

AF:

0.000153

AC:

AN:

111169

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

AN XY:

33375

show subpopulations

Gnomad4 AFR

AF:

0.000196

Gnomad4 AMR

AF:

0.000191

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00172

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000566

Gnomad4 OTH

AF:

0.00

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 12, 2024

The c.430G>A (p.D144N) alteration is located in exon 4 (coding exon 4) of the PUDP gene. This alteration results from a G to A substitution at nucleotide position 430, causing the aspartic acid (D) at amino acid position 144 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-1.0

CADD

Benign

8.4

DANN

Uncertain

0.99

DEOGEN2

Benign

0.043

T;.;.;.;.

FATHMM_MKL

Benign

0.095

LIST_S2

Benign

0.45

T;T;T;T;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.036

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.82

L;.;.;L;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.7

N;N;N;N;N

REVEL

Benign

0.043

Sift

Benign

0.19

T;T;T;T;T

Sift4G

Benign

0.39

T;T;T;T;.

Polyphen

0.0030

B;B;.;P;.

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over