rs143347739

Variant names:

• chr9-34343339-C-A
• rs143347739
• NM_001161.5:c.343C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-34343339-C-A
• chr9-34343339-C-G
• chr9-34343339-C-T

Variant summary

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

The NM_001161.5(NUDT2):​c.343C>A​(p.Arg115Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,580 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R115C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: NUDT2 NM_001161.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.86

Genes affected

NUDT2 (HGNC:8049): (nudix hydrolase 2) This gene encodes a member of the MutT family of nucleotide pyrophosphatases, a subset of the larger NUDIX hydrolase family. The gene product possesses a modification of the MutT sequence motif found in certain nucleotide pyrophosphatases. The enzyme asymmetrically hydrolyzes Ap4A to yield AMP and ATP and is responsible for maintaining the intracellular level of the dinucleotide Ap4A, the function of which has yet to be established. This gene may be a candidate tumor suppressor gene. Alternative splicing has been observed at this locus and four transcript variants, all encoding the same protein, have been identified. [provided by RefSeq, Sep 2011]

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
NUDT2	NM_001161.5	c.343C>A	p.Arg115Ser	missense_variant	Exon 5 of 5	ENST00000379158.7	NP_001152.1
NUDT2	NM_001244390.2	c.343C>A	p.Arg115Ser	missense_variant	Exon 3 of 3		NP_001231319.1
NUDT2	NM_147172.3	c.343C>A	p.Arg115Ser	missense_variant	Exon 5 of 5		NP_671701.1
NUDT2	NM_147173.3	c.343C>A	p.Arg115Ser	missense_variant	Exon 4 of 4		NP_671702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUDT2	ENST00000379158.7	c.343C>A	p.Arg115Ser	missense_variant	Exon 5 of 5	3	NM_001161.5	ENSP00000368455.1
NUDT2	ENST00000346365.8	c.343C>A	p.Arg115Ser	missense_variant	Exon 4 of 4	1		ENSP00000344187.4
NUDT2	ENST00000379155.9	c.343C>A	p.Arg115Ser	missense_variant	Exon 5 of 5	3		ENSP00000368452.5
NUDT2	ENST00000618590.1	c.343C>A	p.Arg115Ser	missense_variant	Exon 3 of 3	3		ENSP00000482384.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461580 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727082

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.047	T;T;T;T
Eigen	Benign	0.15
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	.;.;D;.
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.62	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.9	M;M;M;M
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.0	D;D;.;D
REVEL	Benign	0.27
Sift	Uncertain	0.016	D;D;.;D
Sift4G	Benign	0.10	T;T;T;T
Polyphen		0.93	P;P;P;P
Vest4		0.57
MutPred		0.65		Gain of disorder (P = 0.1421);Gain of disorder (P = 0.1421);Gain of disorder (P = 0.1421);Gain of disorder (P = 0.1421);
MVP		0.23
MPC		1.3
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.91
gMVP		0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs143347739; hg19: chr9-34343337;