Variant X-7105631-G-A 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.269C>T(p.Ala90Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000951 in 1,202,050 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 369 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00048 ( 0 hom., 17 hem., cov: 23)

Exomes 𝑓: 0.0010 ( 0 hom. 352 hem. )

Consequence

PUDP
NM_012080.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.116

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.029144347).

BS2

High Hemizygotes in GnomAd4 at 17 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PUDP	NM_012080.5 linkuse as main transcript	c.269C>T	p.Ala90Val	missense_variant	2/4	ENST00000381077.10	NP_036212.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PUDP	ENST00000381077.10 linkuse as main transcript	c.269C>T	p.Ala90Val	missense_variant	2/4	1	NM_012080.5	ENSP00000370467	P1	Q08623-1

Frequencies

GnomAD3 genomes

AF:

0.000484

AC:

AN:

111625

Hom.:

Cov.:

AF XY:

0.000503

AC XY:

AN XY:

33813

show subpopulations

Gnomad AFR

AF:

0.000195

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000286

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000378

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000827

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000461

AC:

AN:

171468

Hom.:

AF XY:

0.000413

AC XY:

AN XY:

58120

show subpopulations

Gnomad AFR exome

AF:

0.0000826

Gnomad AMR exome

AF:

0.0000765

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000365

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000844

Gnomad OTH exome

AF:

0.00118

GnomAD4 exome

AF:

0.000999

AC:

1089

AN:

1090374

Hom.:

Cov.:

AF XY:

0.000986

AC XY:

352

AN XY:

357048

show subpopulations

Gnomad4 AFR exome

AF:

0.0000763

Gnomad4 AMR exome

AF:

0.000202

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000264

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00123

Gnomad4 OTH exome

AF:

0.000853

GnomAD4 genome

AF:

0.000484

AC:

AN:

111676

Hom.:

Cov.:

AF XY:

0.000502

AC XY:

AN XY:

33874

show subpopulations

Gnomad4 AFR

AF:

0.000195

Gnomad4 AMR

AF:

0.000285

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000379

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000827

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000760

Hom.:

Bravo

AF:

0.000484

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00242

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00123

AC:

ExAC

AF:

0.000447

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

Apr 07, 2022

The c.338C>T (p.A113V) alteration is located in exon 3 (coding exon 3) of the PUDP gene. This alteration results from a C to T substitution at nucleotide position 338, causing the alanine (A) at amino acid position 113 to be replaced by a valine (V). 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

0.11

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.35

DANN

Benign

0.96

DEOGEN2

Benign

0.049

T;.;.;.

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.77

T;T;T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.029

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.4

L;.;L;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.7

N;N;N;N

REVEL

Benign

0.016

Sift

Benign

0.30

T;T;T;T

Sift4G

Benign

0.25

T;T;T;.

Polyphen

0.17

B;.;D;P

Vest4

0.095

MVP

0.13

MPC

0.066

ClinPred

0.013

GERP RS

2.1

Varity_R

0.13

gMVP

0.42

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