6-34383990-G-A

Position:

• chr6-34383990-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006703.4(NUDT3):​c.99+8274C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0736 in 152,228 control chromosomes in the GnomAD database, including 1,216 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.074 (1216 hom., cov: 31)
• Consequence: NUDT3 NM_006703.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.475

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUDT3	NM_006703.4	c.99+8274C>T		intron_variant		ENST00000607016.2	NP_006694.1
RPS10-NUDT3	NM_001202470.3	c.456+34379C>T		intron_variant			NP_001189399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUDT3	ENST00000607016.2	c.99+8274C>T		intron_variant		1	NM_006703.4	ENSP00000476119.1
RPS10-NUDT3	ENST00000639725.1	c.456+34379C>T		intron_variant		5		ENSP00000492441.1
RPS10-NUDT3	ENST00000639877.1	c.456+34379C>T		intron_variant		5		ENSP00000491891.1
RPS10-NUDT3	ENST00000605528.2	c.381+34379C>T		intron_variant		5		ENSP00000475027.2

Frequencies

GnomAD3 genomes AF: 0.0736 AC: 11192 AN: 152110 Hom.: 1208 Cov.: 31

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.0890

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.0690

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.0814

Gnomad MID AF: 0.0541

Gnomad NFE AF: 0.0396

Gnomad OTH AF: 0.0880

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0736 AC: 11203 AN: 152228 Hom.: 1216 Cov.: 31 AF XY: 0.0820 AC XY: 6100 AN XY: 74420

Gnomad4 AFR AF: 0.0141

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.0690

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.0814

Gnomad4 NFE AF: 0.0396

Gnomad4 OTH AF: 0.0880

Alfa AF: 0.0751 Hom.: 223

Bravo AF: 0.0853

Asia WGS AF: 0.286 AC: 992 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.32
DANN	Benign	0.73

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: rs3778077; hg19: chr6-34351767;