Genetic Variant NUDT8:p.Arg42Leu (chr11-67629787-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001243750.2(NUDT8):c.125G>T(p.Arg42Leu) 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. 13/22 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)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NUDT8
NM_001243750.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.604

Publications

0 publications found

Variant links:

Genes affected

NUDT8 (HGNC:8055): (nudix hydrolase 8) Predicted to enable magnesium ion binding activity and manganese ion binding activity. Predicted to be involved in purine nucleoside bisphosphate catabolic process. Predicted to be located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

NUDT8 links:

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ACMG classification

Classification was made for transcript

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=0.1456598).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243750.2. 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
	NUDT8	NM_001243750.2	MANE Select	c.125G>T	p.Arg42Leu	missense	Exon 1 of 4	NP_001230679.1	Q8WV74-1
	NUDT8	NM_181843.3		c.125G>T	p.Arg42Leu	missense	Exon 1 of 3	NP_862826.1	Q8WV74-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NUDT8	ENST00000376693.3	TSL:2 MANE Select	c.125G>T	p.Arg42Leu	missense	Exon 1 of 4	ENSP00000365883.2	Q8WV74-1
NUDT8	ENST00000301490.8	TSL:1	c.125G>T	p.Arg42Leu	missense	Exon 1 of 3	ENSP00000301490.4	Q8WV74-2
NUDT8	ENST00000943310.1		c.125G>T	p.Arg42Leu	missense	Exon 1 of 5	ENSP00000613369.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1371292

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

682332

African (AFR)

AF:

0.00

AC:

AN:

28412

American (AMR)

AF:

0.00

AC:

AN:

35374

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24030

East Asian (EAS)

AF:

0.00

AC:

AN:

31724

South Asian (SAS)

AF:

0.00

AC:

AN:

78206

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37874

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4016

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1075428

Other (OTH)

AF:

0.00

AC:

AN:

56228

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.045

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.80

M_CAP

Pathogenic

0.38

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

-0.60

PrimateAI

Pathogenic

0.94

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.045

Sift

Benign

0.11

Sift4G

Benign

0.23

Polyphen

0.016

Vest4

0.31

MutPred

0.42

Loss of MoRF binding (P = 0.0116)

MVP

0.092

MPC

0.34

ClinPred

0.84

GERP RS

2.0

PromoterAI

0.031

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.18

gMVP

0.18

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over