rs146519172

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014142.4(NUDT5):c.386C>T(p.Ala129Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000578 in 1,608,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A129T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

NUDT5
NM_014142.4 missense, splice_region

Scores

Splicing: ADA: 0.0001212

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.482

Publications

1 publications found

Variant links:

Genes affected

NUDT5 (HGNC:8052): (nudix hydrolase 5) This gene belongs to the Nudix (nucleoside diphosphate linked moiety X) hydrolase superfamily. The encoded enzyme catalyzes the hydrolysis of modified nucleoside diphosphates, including ADP-ribose (ADPR) and 8-oxoGua-containing 8-oxo-dADP and 8-oxo-dGDP. Protein-bound ADP ribose can be hazardous to the cell because it can modify some amino acid residues, resulting in the inhibition of ATP-activated potassium channels. 8-oxoGua is an oxidized form of guanine that can potentially alter genetic information by pairing with adenine and cytosine in RNA. Presence of 8-oxoGua in RNA results in formation of abnormal proteins due to translational errors. [provided by RefSeq, Aug 2013]

NUDT5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.058387727).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014142.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NUDT5	NM_014142.4	MANE Select	c.386C>T	p.Ala129Val	missense splice_region	Exon 7 of 10	NP_054861.2
NUDT5	NM_001321647.2		c.386C>T	p.Ala129Val	missense splice_region	Exon 7 of 9	NP_001308576.1
NUDT5	NM_001321648.2		c.128C>T	p.Ala43Val	missense splice_region	Exon 8 of 11	NP_001308577.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NUDT5	ENST00000491614.6	TSL:1 MANE Select	c.386C>T	p.Ala129Val	missense splice_region	Exon 7 of 10	ENSP00000419628.1	Q9UKK9
NUDT5	ENST00000378937.7	TSL:3	c.425C>T	p.Ala142Val	missense splice_region	Exon 8 of 11	ENSP00000368219.3	A6NFX8
NUDT5	ENST00000905393.1		c.386C>T	p.Ala129Val	missense splice_region	Exon 7 of 10	ENSP00000575452.1

Frequencies

GnomAD3 genomes

AF:

0.000144

AC:

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

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:

0.00633

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000760

AC:

AN:

249842

AF XY:

0.0000741

show subpopulations

Gnomad AFR exome

AF:

0.000370

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.0000708

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000495

AC:

AN:

1455788

Hom.:

Cov.:

AF XY:

0.0000524

AC XY:

AN XY:

724504

show subpopulations

African (AFR)

AF:

0.000300

AC:

AN:

33362

American (AMR)

AF:

0.00

AC:

AN:

44612

Ashkenazi Jewish (ASJ)

AF:

0.000115

AC:

AN:

26088

East Asian (EAS)

AF:

0.00

AC:

AN:

39642

South Asian (SAS)

AF:

0.0000698

AC:

AN:

85986

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.0000425

AC:

AN:

1106754

Other (OTH)

AF:

0.0000498

AC:

AN:

60190

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000138

AC:

AN:

152370

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74512

show subpopulations

African (AFR)

AF:

0.000409

AC:

AN:

41580

American (AMR)

AF:

0.00

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68036

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000135

Hom.:

Bravo

AF:

0.000151

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000659

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.20

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.81

M_CAP

Benign

0.0083

MetaRNN

Benign

0.058

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.0

PhyloP100

0.48

PrimateAI

Benign

0.38

PROVEAN

Benign

0.50

REVEL

Benign

0.029

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.11

Vest4

0.28

MVP

0.23

MPC

0.29

ClinPred

0.010

GERP RS

0.38

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.041

gMVP

0.50

Mutation Taster

=70/30

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00012

dbscSNV1_RF

Benign

0.072

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over