chr6-34288764-C-A

Variant names:

• chr6-34288764-C-A
• NM_006703.4:c.508G>T

Variant summary

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

The NM_006703.4(NUDT3):​c.508G>T​(p.Gly170Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NUDT3 NM_006703.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.80
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20998645).

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.508G>T	p.Gly170Cys	missense	Exon 5 of 5	NP_006694.1	O95989
	RPS10-NUDT3	NM_001202470.3		c.865G>T	p.Gly289Cys	missense	Exon 9 of 9	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.508G>T	p.Gly170Cys	missense	Exon 5 of 5	ENSP00000476119.1	O95989
	RPS10-NUDT3	ENST00000639725.1	TSL:5	c.865G>T	p.Gly289Cys	missense	Exon 9 of 9	ENSP00000492441.1	A0A1W2PQS6
	RPS10-NUDT3	ENST00000639877.1	TSL:5	c.865G>T	p.Gly289Cys	missense	Exon 9 of 9	ENSP00000491891.1	A0A1W2PQS6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	0.093
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	20
DANN	Uncertain	0.97
DEOGEN2	Benign	0.092	T
Eigen	Benign	-0.028
Eigen_PC	Benign	0.081
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.8
PrimateAI	Benign	0.45	T
Sift4G	Uncertain	0.024	D
Polyphen		0.94	P
Vest4		0.28
MutPred		0.30		Gain of catalytic residue at M168 (P = 4e-04)
MVP		0.27
MPC		0.79
ClinPred		0.89	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.73
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

hg19: chr6-34256541;