Variant X-7050303-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_012080.5(PUDP):c.680A>G(p.Tyr227Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000538 in 1,208,319 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000055 ( 0 hom. 17 hem. )

Consequence

PUDP
NM_012080.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.470

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10856435).

BS2

High Hemizygotes in GnomAdExome4 at 17 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PUDP	NM_012080.5 linkuse as main transcript	c.680A>G	p.Tyr227Cys	missense_variant	4/4	ENST00000381077.10	NP_036212.3	Q08623-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PUDP	ENST00000381077.10 linkuse as main transcript	c.680A>G	p.Tyr227Cys	missense_variant	4/4	1	NM_012080.5	ENSP00000370467.6	Q08623-1
PUDP	ENST00000424830.6 linkuse as main transcript	c.749A>G	p.Tyr250Cys	missense_variant	5/5	3		ENSP00000396452.2	Q08623-4
PUDP	ENST00000412827.6 linkuse as main transcript	c.551A>G	p.Tyr184Cys	missense_variant	4/4	2		ENSP00000406260.2	Q08623-2
PUDP	ENST00000655425.1 linkuse as main transcript	n.204+26917A>G		intron_variant				ENSP00000499460.1	A0A590UJH7

Frequencies

GnomAD3 genomes

AF:

0.0000447

AC:

AN:

111767

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33965

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000284

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000890

AC:

AN:

179746

Hom.:

AF XY:

0.0000911

AC XY:

AN XY:

65882

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000111

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.000681

GnomAD4 exome

AF:

0.0000547

AC:

AN:

1096499

Hom.:

Cov.:

AF XY:

0.0000470

AC XY:

AN XY:

362011

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000227

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000547

Gnomad4 OTH exome

AF:

0.0000869

GnomAD4 genome

AF:

0.0000447

AC:

AN:

111820

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34028

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000283

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000604

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ExAC

AF:

0.0000745

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

Dec 18, 2023

The c.749A>G (p.Y250C) alteration is located in exon 5 (coding exon 5) of the PUDP gene. This alteration results from a A to G substitution at nucleotide position 749, causing the tyrosine (Y) at amino acid position 250 to be replaced by a cysteine (C). 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

0.29

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.27

T;.;.

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.39

T;T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Pathogenic

3.2

M;.;.

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-6.6

D;D;D

REVEL

Benign

0.11

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.40

MVP

0.055

MPC

0.16

ClinPred

0.54

GERP RS

-2.5

Varity_R

0.82

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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