Variant X-7077377-G-A 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.353C>T(p.Ala118Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000141 in 1,208,780 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 4 hem., cov: 22)

Exomes 𝑓: 0.000012 ( 0 hom. 4 hem. )

Consequence

PUDP
NM_012080.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.26

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=0.08056876).

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PUDP	NM_012080.5 linkuse as main transcript	c.353C>T	p.Ala118Val	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.353C>T	p.Ala118Val	missense_variant	3/4	1	NM_012080.5	ENSP00000370467.6		Q08623-1

Frequencies

GnomAD3 genomes

AF:

0.0000360

AC:

AN:

111045

Hom.:

Cov.:

AF XY:

0.000120

AC XY:

AN XY:

33243

show subpopulations

Gnomad AFR

AF:

0.0000327

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000566

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000277

AC:

AN:

180705

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

66751

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000741

Gnomad SAS exome

AF:

0.0000528

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000371

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000118

AC:

AN:

1097735

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

363169

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000131

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000360

AC:

AN:

111045

Hom.:

Cov.:

AF XY:

0.000120

AC XY:

AN XY:

33243

show subpopulations

Gnomad4 AFR

AF:

0.0000327

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000566

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000595

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 27, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.0020

DANN

Benign

0.60

DEOGEN2

Benign

0.023

T;.;.;.;.

FATHMM_MKL

Benign

0.0097

LIST_S2

Benign

0.33

T;T;T;T;T

M_CAP

Benign

0.00097

MetaRNN

Benign

0.081

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.57

N;.;.;N;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.55

N;N;N;N;N

REVEL

Benign

0.024

Sift

Benign

0.33

T;T;T;T;T

Sift4G

Benign

0.32

T;T;T;T;.

Polyphen

0.0010

B;B;.;B;.

Vest4

0.027

MutPred

0.47

Loss of disorder (P = 0.0704);.;.;Loss of disorder (P = 0.0704);Loss of disorder (P = 0.0704);

MVP

0.048

MPC

0.065

ClinPred

0.050

GERP RS

-7.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.044

gMVP

0.38

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