Variant 10-73126696-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015901.6(NUDT13):c.727C>T(p.Arg243Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 1,613,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

NUDT13
NM_015901.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.653

Variant links:

Genes affected

NUDT13 (HGNC:18827): (nudix hydrolase 13) Predicted to enable NADH pyrophosphatase activity. Predicted to be involved in NADH metabolic process and NADP catabolic process. Predicted to be located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

NUDT13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029321283).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUDT13	NM_015901.6 linkuse as main transcript	c.727C>T	p.Arg243Cys	missense_variant	8/9	ENST00000357321.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUDT13	ENST00000357321.9 linkuse as main transcript	c.727C>T	p.Arg243Cys	missense_variant	8/9	5	NM_015901.6	P1	Q86X67-1

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000183

AC:

AN:

251376

Hom.:

AF XY:

0.000191

AC XY:

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00347

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000104

AC:

152

AN:

1461822

Hom.:

Cov.:

AF XY:

0.000114

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00394

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.000281

GnomAD4 genome

AF:

0.000210

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000461

Hom.:

Bravo

AF:

0.000212

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000148

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Dec 19, 2022

The c.727C>T (p.R243C) alteration is located in exon 8 (coding exon 7) of the NUDT13 gene. This alteration results from a C to T substitution at nucleotide position 727, causing the arginine (R) at amino acid position 243 to be replaced by a cysteine (C). 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

0.090

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.21

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.029

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.62

D;N;N;N;N

PrimateAI

Benign

0.23

PROVEAN

Pathogenic

-5.0

D;D;D

REVEL

Benign

0.11

Sift

Benign

0.043

D;D;D

Sift4G

Uncertain

0.027

D;D;D

Polyphen

0.19

.;.;B

Vest4

0.28

MVP

0.35

MPC

0.11

ClinPred

0.21

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.25

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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