rs3778077

Variant names:

• chr6-34383990-G-A
• rs3778077
• NM_006703.4:c.99+8274C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDT3	NM_006703.4	MANE Select	c.99+8274C>T		intron	N/A	NP_006694.1
	RPS10-NUDT3	NM_001202470.3		c.456+34379C>T		intron	N/A	NP_001189399.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDT3	ENST00000607016.2	TSL:1 MANE Select	c.99+8274C>T		intron	N/A	ENSP00000476119.1
	RPS10-NUDT3	ENST00000639725.1	TSL:5	c.456+34379C>T		intron	N/A	ENSP00000492441.1
	RPS10-NUDT3	ENST00000639877.1	TSL:5	c.456+34379C>T		intron	N/A	ENSP00000491891.1

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

African (AFR) AF: 0.0141 AC: 585 AN: 41576

American (AMR) AF: 0.220 AC: 3360 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0690 AC: 239 AN: 3466

East Asian (EAS) AF: 0.426 AC: 2195 AN: 5154

South Asian (SAS) AF: 0.204 AC: 985 AN: 4820

European-Finnish (FIN) AF: 0.0814 AC: 863 AN: 10598

Middle Eastern (MID) AF: 0.0582 AC: 17 AN: 292

European-Non Finnish (NFE) AF: 0.0396 AC: 2692 AN: 68022

Other (OTH) AF: 0.0880 AC: 186 AN: 2114

Alfa AF: 0.0737 Hom.: 223

Bravo AF: 0.0853

Asia WGS AF: 0.286 AC: 992 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.32
DANN	Benign	0.73
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

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: rs3778077; hg19: chr6-34351767;