10-12184892-G-C

Variant names:

• chr10-12184892-G-C
• rs543267377
• NM_014142.4:c.128C>G

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.78

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]

ACMG classification

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	c.128C>G	p.Thr43Ser	missense_variant	Exon 3 of 10	ENST00000491614.6	NP_054861.2
NUDT5	NM_001321647.2	c.128C>G	p.Thr43Ser	missense_variant	Exon 3 of 9		NP_001308576.1
NUDT5	NM_001321648.2	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	c.128C>G	p.Thr43Ser	missense_variant	Exon 3 of 10	1	NM_014142.4	ENSP00000419628.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000845 AC: 2 AN: 236806 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 127448

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: 2 AN: 1379082 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 686590

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.: 33

ExAC AF: 0.0000165 AC: 2

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	T
BayesDel_noAF	Benign	-0.46
CADD	Pathogenic	27
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	D
LIST_S2	Benign	0.34	.;T;T;D;D;D
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.12	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.;L;.;.;.
PrimateAI	Uncertain	0.52	T
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	T
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

Other links and lift over

dbSNP: rs543267377; hg19: chr10-12226891;