Variant 7-2249951-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NUDT1	NM_002452.4 linkuse as main transcript	c.247G>A	p.Val83Met	missense_variant	3/4	ENST00000356714.6	NP_002443.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUDT1	ENST00000356714.6 linkuse as main transcript	c.247G>A	p.Val83Met	missense_variant	3/4	1	NM_002452.4	ENSP00000349148	P1	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

GnomAD3 exomes

AF:

0.0215

AC:

5408

AN:

251386

Hom.:

113

AF XY:

0.0222

AC XY:

3017

AN XY:

135892

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 SAS exome

AF:

0.0281

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

Gnomad4 AFR exome

AF:

0.0181

Gnomad4 AMR exome

AF:

0.00637

Gnomad4 ASJ exome

AF:

0.0580

Gnomad4 EAS exome

AF:

0.0694

Gnomad4 SAS exome

AF:

0.0282

Gnomad4 FIN exome

AF:

0.0627

Gnomad4 NFE exome

AF:

0.00698

Gnomad4 OTH exome

AF:

0.0182

GnomAD4 genome

AF:

0.0183

AC:

2782

AN:

152344

Hom.:

Cov.:

AF XY:

0.0216

AC XY:

1609

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0155

Gnomad4 AMR

AF:

0.0114

Gnomad4 ASJ

AF:

0.0513

Gnomad4 EAS

AF:

0.0407

Gnomad4 SAS

AF:

0.0281

Gnomad4 FIN

AF:

0.0706

Gnomad4 NFE

AF:

0.00944

Gnomad4 OTH

AF:

0.0208

Alfa

AF:

0.0134

Hom.:

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

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.40

CADD

Benign

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

MutationTaster

Benign

1.0

D;D;D;D;D;D

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

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over