NM_014142.4:c.261G>C

Variant names:

• chr10-12177821-C-G
• rs149162963
• NM_014142.4:c.261G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014142.4(NUDT5):​c.261G>C​(p.Met87Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000282 in 1,614,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00029 (0 hom.)
• Consequence: NUDT5 NM_014142.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.56
• Publications: 3 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.027803302).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014142.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDT5	NM_014142.4	MANE Select	c.261G>C	p.Met87Ile	missense	Exon 5 of 10	NP_054861.2
	NUDT5	NM_001321648.2		c.3G>C	p.Met1?	start_lost	Exon 6 of 11	NP_001308577.1
	NUDT5	NM_001321647.2		c.261G>C	p.Met87Ile	missense	Exon 5 of 9	NP_001308576.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDT5	ENST00000491614.6	TSL:1 MANE Select	c.261G>C	p.Met87Ile	missense	Exon 5 of 10	ENSP00000419628.1	Q9UKK9
	NUDT5	ENST00000378937.7	TSL:3	c.300G>C	p.Met100Ile	missense	Exon 6 of 11	ENSP00000368219.3	A6NFX8
	NUDT5	ENST00000905393.1		c.261G>C	p.Met87Ile	missense	Exon 5 of 10	ENSP00000575452.1

Frequencies

GnomAD3 genomes AF: 0.000243 AC: 37 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000255 AC: 64 AN: 251422 AF XY: 0.000287

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000173

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000440

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000286 AC: 418 AN: 1461774 Hom.: 0 Cov.: 30 AF XY: 0.000307 AC XY: 223 AN XY: 727192

African (AFR) AF: 0.0000597 AC: 2 AN: 33478

American (AMR) AF: 0.000134 AC: 6 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000255 AC: 22 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00329 AC: 19 AN: 5768

European-Non Finnish (NFE) AF: 0.000308 AC: 342 AN: 1111900

Other (OTH) AF: 0.000447 AC: 27 AN: 60396

GnomAD4 genome AF: 0.000243 AC: 37 AN: 152306 Hom.: 0 Cov.: 32 AF XY: 0.000201 AC XY: 15 AN XY: 74470

African (AFR) AF: 0.00 AC: 0 AN: 41562

American (AMR) AF: 0.000458 AC: 7 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000375 Hom.: 0

Bravo AF: 0.000230

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000272 AC: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.00124

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	15
DANN	Benign	0.78
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.53
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.62	N
PhyloP100		1.6
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.040
Sift	Benign	1.0	T
Sift4G	Benign	0.90	T
Polyphen		0.0010	B
Vest4		0.29
MutPred		0.46		Gain of catalytic residue at M87 (P = 0.1814)
MVP		0.48
MPC		0.32
ClinPred		0.014	T
GERP RS		2.9
Varity_R		0.15
gMVP		0.42
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs149162963; hg19: chr10-12219820; COSMIC: COSV66719059; COSMIC: COSV66719059;