NM_014142.4:c.128C>T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014142.4(NUDT5):​c.128C>T​(p.Thr43Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000457 in 1,530,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000044 (0 hom.)
• Consequence: NUDT5 NM_014142.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.78
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18602768).

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.128C>T	p.Thr43Ile	missense	Exon 3 of 10	NP_054861.2
	NUDT5	NM_001321647.2		c.128C>T	p.Thr43Ile	missense	Exon 3 of 9	NP_001308576.1
	NUDT5	NM_001321648.2		c.-226C>T		5_prime_UTR	Exon 3 of 11	NP_001308577.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDT5	ENST00000491614.6	TSL:1 MANE Select	c.128C>T	p.Thr43Ile	missense	Exon 3 of 10	ENSP00000419628.1	Q9UKK9
	NUDT5	ENST00000378937.7	TSL:3	c.128C>T	p.Thr43Ile	missense	Exon 3 of 11	ENSP00000368219.3	A6NFX8
	NUDT5	ENST00000905393.1		c.128C>T	p.Thr43Ile	missense	Exon 3 of 10	ENSP00000575452.1

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151538 Hom.: 0 Cov.: 33

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000422 AC: 1 AN: 236806 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000912

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000435 AC: 6 AN: 1379082 Hom.: 0 Cov.: 25 AF XY: 0.00000583 AC XY: 4 AN XY: 686590

African (AFR) AF: 0.00 AC: 0 AN: 30638

American (AMR) AF: 0.00 AC: 0 AN: 39980

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24078

East Asian (EAS) AF: 0.00 AC: 0 AN: 36088

South Asian (SAS) AF: 0.00 AC: 0 AN: 79190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5442

European-Non Finnish (NFE) AF: 0.00000568 AC: 6 AN: 1056240

Other (OTH) AF: 0.00 AC: 0 AN: 56086

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151538 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 73994

African (AFR) AF: 0.00 AC: 0 AN: 41328

American (AMR) AF: 0.00 AC: 0 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.00 AC: 0 AN: 4768

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10440

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67888

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

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	Benign	0.10
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T
Eigen	Benign	-0.042
Eigen_PC	Benign	0.089
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		3.8
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.096
Sift	Benign	0.13	T
Sift4G	Benign	0.11	T
Polyphen		0.0020	B
Vest4		0.15
MVP		0.38
MPC		0.31
ClinPred		0.34	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.48
Mutation Taster		=55/45	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs543267377; hg19: chr10-12226891;