chr6-34288761-T-A

Position:

• chr6-34288761-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006703.4(NUDT3):​c.511A>T​(p.Ile171Phe) 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. 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: 3.58

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2573876).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUDT3	NM_006703.4	c.511A>T	p.Ile171Phe	missense_variant	5/5	ENST00000607016.2	NP_006694.1
RPS10-NUDT3	NM_001202470.3	c.868A>T	p.Ile290Phe	missense_variant	9/9		NP_001189399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUDT3	ENST00000607016.2	c.511A>T	p.Ile171Phe	missense_variant	5/5	1	NM_006703.4	ENSP00000476119.1
RPS10-NUDT3	ENST00000639725.1	c.868A>T	p.Ile290Phe	missense_variant	9/9	5		ENSP00000492441.1
RPS10-NUDT3	ENST00000639877.1	c.868A>T	p.Ile290Phe	missense_variant	9/9	5		ENSP00000491891.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 06, 2022

The c.511A>T (p.I171F) alteration is located in exon 5 (coding exon 5) of the NUDT3 gene. This alteration results from a A to T substitution at nucleotide position 511, causing the isoleucine (I) at amino acid position 171 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.093	T;.;.
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.53	T;.;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	M;.;.
PrimateAI	Uncertain	0.62	T
Sift4G	Uncertain	0.016	D;.;.
Polyphen		0.72	P;.;.
Vest4		0.62
MutPred		0.19		Loss of sheet (P = 0.0315);.;.;
MVP		0.20
MPC		1.3
ClinPred		0.85	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1431997363; hg19: chr6-34256538;