Genetic Variant NM_014142.4:c.128C>G (chr10-12184892-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014142.4(NUDT5):c.128C>G(p.Thr43Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000145 in 1,379,082 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

NUDT5
NM_014142.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.78

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUDT5	NM_014142.4 link	c.128C>G	p.Thr43Ser	missense_variant	Exon 3 of 10	ENST00000491614.6	NP_054861.2	Q9UKK9
NUDT5	NM_001321647.2 link	c.128C>G	p.Thr43Ser	missense_variant	Exon 3 of 9		NP_001308576.1
NUDT5	NM_001321648.2 link	c.-226C>G		5_prime_UTR_variant	Exon 3 of 11		NP_001308577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUDT5	ENST00000491614.6 link	c.128C>G	p.Thr43Ser	missense_variant	Exon 3 of 10	1	NM_014142.4	ENSP00000419628.1		Q9UKK9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000845

AC:

AN:

236806

Hom.:

AF XY:

0.00

AC XY:

AN XY:

127448

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:

0.00

Gnomad NFE exome

AF:

0.0000182

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000145

AC:

AN:

1379082

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

686590

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:

0.00

Gnomad4 NFE exome

AF:

0.00000189

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.46

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.27

T;.;T;.;T;.

Eigen

Benign

-0.11

Eigen_PC

Benign

0.035

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.34

.;T;T;D;D;D

M_CAP

Benign

0.0075

MetaRNN

Benign

0.12

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;.;L;.;.;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.81

N;N;N;N;N;N

REVEL

Benign

0.072

Sift

Benign

0.32

T;T;T;T;T;T

Sift4G

Benign

0.56

T;T;T;T;T;.

Polyphen

0.018

B;.;B;.;B;.

Vest4

0.23

MutPred

0.26

Gain of phosphorylation at T43 (P = 0.0696);Gain of phosphorylation at T43 (P = 0.0696);Gain of phosphorylation at T43 (P = 0.0696);Gain of phosphorylation at T43 (P = 0.0696);Gain of phosphorylation at T43 (P = 0.0696);Gain of phosphorylation at T43 (P = 0.0696);

MVP

0.39

MPC

0.26

ClinPred

0.13

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.97

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.97

Position offset: 1

DS_DL_spliceai

0.48

Position offset: -3

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