NM_006703.4:c.65C>G

Variant names:

• chr6-34392298-G-C
• rs547100994
• NM_006703.4:c.65C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006703.4(NUDT3):​c.65C>G​(p.Ala22Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000249 in 1,605,678 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 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NUDT3 NM_006703.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.84
• Publications: 4 publications found

Genes affected

NUDT3 (HGNC:8050): (nudix hydrolase 3) NUDT3 belongs to the MutT, or Nudix, protein family. Nudix proteins act as homeostatic checkpoints at important stages in nucleoside phosphate metabolic pathways, guarding against elevated levels of potentially dangerous intermediates, like 8-oxo-dGTP, which promotes AT-to-CG transversions (Safrany et al., 1998 [PubMed 9822604]).[supplied by OMIM, Feb 2011]

RPS10-NUDT3 (HGNC:49181): (RPS10-NUDT3 readthrough) This locus represents naturally occurring read-through transcription between the neighboring RPS10 (ribosomal protein S10) and NUDT3 (nudix (nucleoside diphosphate linked moiety X)-type motif 3) genes on chromosome 6. The read-through transcript produces a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3069017).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006703.4. 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
	NUDT3	NM_006703.4	MANE Select	c.65C>G	p.Ala22Gly	missense	Exon 1 of 5	NP_006694.1	O95989
	RPS10-NUDT3	NM_001202470.3		c.456+26071C>G		intron	N/A	NP_001189399.1	A0A1W2PQS6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDT3	ENST00000607016.2	TSL:1 MANE Select	c.65C>G	p.Ala22Gly	missense	Exon 1 of 5	ENSP00000476119.1	O95989
	RPS10-NUDT3	ENST00000639725.1	TSL:5	c.456+26071C>G		intron	N/A	ENSP00000492441.1	A0A1W2PQS6
	NUDT3	ENST00000914238.1		c.65C>G	p.Ala22Gly	missense	Exon 1 of 5	ENSP00000584297.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152110 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000855 AC: 2 AN: 233918 AF XY: 0.0000156

Gnomad AFR exome AF: 0.000142

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453460 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 723270

African (AFR) AF: 0.0000309 AC: 1 AN: 32312

American (AMR) AF: 0.00 AC: 0 AN: 44430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25904

East Asian (EAS) AF: 0.00 AC: 0 AN: 39036

South Asian (SAS) AF: 0.00 AC: 0 AN: 85742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50666

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109544

Other (OTH) AF: 0.00 AC: 0 AN: 60084

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152218 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74424

African (AFR) AF: 0.0000722 AC: 3 AN: 41540

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000166 AC: 2

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	Uncertain	0.56
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Benign	0.66	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.085	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		6.8
Sift4G	Benign	0.31	T
Polyphen		0.97	D
Vest4		0.40
MVP		0.38
MPC		0.77
ClinPred		0.64	D
GERP RS		3.4
PromoterAI		0.080	Neutral
Varity_R		0.49
gMVP		0.80
Mutation Taster		=28/72	disease causing

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: rs547100994; hg19: chr6-34360075;