dbSNP rs4866: NUDT1:p.Val83Met (chr7-2249951-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002452.4(NUDT1):c.247G>A(p.Val83Met) variant causes a missense change. The variant allele was found at a frequency of 0.0141 in 1,614,176 control chromosomes in the GnomAD database, including 475 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.018 ( 57 hom., cov: 33)

Exomes 𝑓: 0.014 ( 418 hom. )

Consequence

NUDT1
NM_002452.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.77

Publications

27 publications found

Variant links:

Genes affected

NUDT1 (HGNC:8048): (nudix hydrolase 1) Misincorporation of oxidized nucleoside triphosphates into DNA/RNA during replication and transcription can cause mutations that may result in carcinogenesis or neurodegeneration. The protein encoded by this gene is an enzyme that hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-dGTP, 8-oxo-dATP, 2-hydroxy-dATP, and 2-hydroxy rATP, to monophosphates, thereby preventing misincorporation. The encoded protein is localized mainly in the cytoplasm, with some in the mitochondria, suggesting that it is involved in the sanitization of nucleotide pools both for nuclear and mitochondrial genomes. Several alternatively spliced transcript variants, some of which encode distinct isoforms, have been identified. Additional variants have been observed, but their full-length natures have not been determined. A rare single-nucleotide polymorphism that results in the production of an additional, longer isoform (p26) has been described. [provided by RefSeq, Dec 2018]

NUDT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0068998635).

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUDT1	NM_002452.4 link	c.247G>A	p.Val83Met	missense_variant	Exon 3 of 4	ENST00000356714.6	NP_002443.3	P36639-4A0A024R819

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUDT1	ENST00000356714.6 link	c.247G>A	p.Val83Met	missense_variant	Exon 3 of 4	1	NM_002452.4	ENSP00000349148.1		P36639-4

Frequencies

GnomAD3 genomes

AF:

0.0182

AC:

2776

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0155

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0114

Gnomad ASJ

AF:

0.0513

Gnomad EAS

AF:

0.0406

Gnomad SAS

AF:

0.0279

Gnomad FIN

AF:

0.0706

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00944

Gnomad OTH

AF:

0.0196

GnomAD2 exomes

AF:

0.0215

AC:

5408

AN:

251386

AF XY:

0.0222

show subpopulations

Gnomad AFR exome

AF:

0.0151

Gnomad AMR exome

AF:

0.00604

Gnomad ASJ exome

AF:

0.0586

Gnomad EAS exome

AF:

0.0359

Gnomad FIN exome

AF:

0.0669

Gnomad NFE exome

AF:

0.0111

Gnomad OTH exome

AF:

0.0225

GnomAD4 exome

AF:

0.0137

AC:

19999

AN:

1461832

Hom.:

418

Cov.:

AF XY:

0.0144

AC XY:

10507

AN XY:

727210

show subpopulations

African (AFR)

AF:

0.0181

AC:

605

AN:

33480

American (AMR)

AF:

0.00637

AC:

285

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0580

AC:

1517

AN:

26136

East Asian (EAS)

AF:

0.0694

AC:

2754

AN:

39700

South Asian (SAS)

AF:

0.0282

AC:

2434

AN:

86258

European-Finnish (FIN)

AF:

0.0627

AC:

3347

AN:

53370

Middle Eastern (MID)

AF:

0.0336

AC:

194

AN:

5768

European-Non Finnish (NFE)

AF:

0.00698

AC:

7766

AN:

1112002

Other (OTH)

AF:

0.0182

AC:

1097

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

1265

2529

3794

5058

6323

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

338

676

1014

1352

1690

<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:

0.0183

AC:

2782

AN:

152344

Hom.:

Cov.:

AF XY:

0.0216

AC XY:

1609

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.0155

AC:

646

AN:

41576

American (AMR)

AF:

0.0114

AC:

174

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0513

AC:

178

AN:

3472

East Asian (EAS)

AF:

0.0407

AC:

211

AN:

5180

South Asian (SAS)

AF:

0.0281

AC:

136

AN:

4834

European-Finnish (FIN)

AF:

0.0706

AC:

750

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00944

AC:

642

AN:

68030

Other (OTH)

AF:

0.0208

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

135

271

406

542

677

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.0132

Hom.:

104

Bravo

AF:

0.0140

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.0120

AC:

ESP6500EA

AF:

0.0100

AC:

ExAC

AF:

0.0206

AC:

2499

Asia WGS

AF:

0.0420

AC:

146

AN:

3478

EpiCase

AF:

0.0138

EpiControl

AF:

0.0145

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.84

.;.;.;T;.;T

MetaRNN

Benign

0.0069

T;T;T;T;T;T

MetaSVM

Benign

-1.1

PhyloP100

5.8

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.7

D;D;D;D;D;.

REVEL

Benign

0.26

Sift

Uncertain

0.019

D;D;T;T;D;.

Sift4G

Benign

0.095

T;T;T;T;T;T

Vest4

0.12

MPC

0.16

ClinPred

0.011

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.78

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over