Variant X-7050367-T-C 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.616A>G(p.Lys206Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000128 in 1,097,751 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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: not found (cov: 23)

Exomes 𝑓: 0.000013 ( 0 hom. 3 hem. )

Consequence

PUDP
NM_012080.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.38

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.039750755).

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PUDP	NM_012080.5 linkuse as main transcript	c.616A>G	p.Lys206Glu	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.616A>G	p.Lys206Glu	missense_variant	4/4	1	NM_012080.5	ENSP00000370467.6	Q08623-1
PUDP	ENST00000424830.6 linkuse as main transcript	c.685A>G	p.Lys229Glu	missense_variant	5/5	3		ENSP00000396452.2	Q08623-4
PUDP	ENST00000412827.6 linkuse as main transcript	c.487A>G	p.Lys163Glu	missense_variant	4/4	2		ENSP00000406260.2	Q08623-2
PUDP	ENST00000655425.1 linkuse as main transcript	n.204+26853A>G		intron_variant				ENSP00000499460.1	A0A590UJH7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000663

AC:

AN:

180944

Hom.:

AF XY:

0.0000299

AC XY:

AN XY:

66988

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000440

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000128

AC:

AN:

1097751

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

363189

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000313

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:

0.00000356

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000248

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

Jun 22, 2021

The c.685A>G (p.K229E) 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 685, causing the lysine (K) at amino acid position 229 to be replaced by a glutamic acid (E). 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

0.21

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.0

DANN

Benign

0.20

DEOGEN2

Benign

0.032

T;.;.

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.82

T;D;T

M_CAP

Benign

0.0033

MetaRNN

Benign

0.040

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.4

L;.;.

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.34

N;N;N

REVEL

Benign

0.025

Sift

Benign

0.95

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.042

MutPred

0.38

Loss of ubiquitination at K206 (P = 0.0148);.;.;

MVP

0.20

MPC

0.091

ClinPred

0.032

GERP RS

2.0

Varity_R

0.15

gMVP

0.54

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