dbSNP rs199672264: NUDT13:p.Arg28Gly (chr10-73114447-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015901.6(NUDT13):c.82C>G(p.Arg28Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000826 in 1,561,292 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R28W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000093 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000082 ( 1 hom. )

Consequence

NUDT13
NM_015901.6 missense, splice_region

Scores

Splicing: ADA: 0.0004214

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.861

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22055921).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUDT13	NM_015901.6 link	c.82C>G	p.Arg28Gly	missense_variant, splice_region_variant	Exon 2 of 9	ENST00000357321.9	NP_056985.3	Q86X67-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUDT13	ENST00000357321.9 link	c.82C>G	p.Arg28Gly	missense_variant, splice_region_variant	Exon 2 of 9	5	NM_015901.6	ENSP00000349874.4		Q86X67-1

Frequencies

GnomAD3 genomes

AF:

0.0000930

AC:

AN:

150610

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000996

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000589

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000185

AC:

AN:

243674

Hom.:

AF XY:

0.000197

AC XY:

AN XY:

131952

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00144

Gnomad NFE exome

AF:

0.000117

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.0000815

AC:

115

AN:

1410682

Hom.:

Cov.:

AF XY:

0.0000855

AC XY:

AN XY:

701460

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00195

Gnomad4 NFE exome

AF:

0.00000926

Gnomad4 OTH exome

AF:

0.0000863

GnomAD4 genome

AF:

0.0000930

AC:

AN:

150610

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

73422

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000996

Gnomad4 NFE

AF:

0.0000589

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000181

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Uncertain

0.058

BayesDel_noAF

Uncertain

0.050

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

.;T;.;.

Eigen

Benign

0.16

Eigen_PC

Benign

0.10

FATHMM_MKL

Benign

0.59

LIST_S2

Uncertain

0.91

D;D;D;D

M_CAP

Benign

0.032

MetaRNN

Benign

0.22

T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.2

.;M;M;M

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-3.4

.;D;D;D

REVEL

Benign

0.25

Sift

Uncertain

0.0030

.;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0, 1.0

.;D;D;.

Vest4

0.76

MVP

0.66

MPC

0.41

ClinPred

0.32

GERP RS

2.1

Varity_R

0.55

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00042

dbscSNV1_RF

Benign

0.14

SpliceAI score (max)

0.33

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.33

Position offset: 1

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