Variant X-51333051-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000356450.3(NUDT10):c.86G>A(p.Arg29His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000645 in 1,208,813 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., 7 hem., cov: 22)

Exomes 𝑓: 0.000045 ( 0 hom. 9 hem. )

Consequence

NUDT10
ENST00000356450.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.409

Variant links:

Genes affected

NUDT10 (HGNC:17621): (nudix hydrolase 10) This gene is a member of the nudix (nucleoside diphosphate linked moiety X)-type motif containing family. The encoded protein is a phosphohydrolase and may regulate the turnover of diphosphoinositol polyphosphates. The turnover of these high-energy diphosphoinositol polyphosphates represents a molecular switching activity with important regulatory consequences. Molecular switching by diphosphoinositol polyphosphates may contribute to the regulation of intracellular trafficking. In some populations putative prostate cancer susceptibility alleles have been identified for this gene. Alternatively spliced transcript variants, which differ only in the 5' UTR, have been found for this gene. [provided by RefSeq, Feb 2015]

NUDT10 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00970158).

BS2

High Hemizygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUDT10	NM_001304963.2 linkuse as main transcript	c.86G>A	p.Arg29His	missense_variant	1/2	ENST00000356450.3	NP_001291892.1
LOC105373204	XR_007068239.1 linkuse as main transcript	n.732-3486C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
NUDT10	ENST00000356450.3 linkuse as main transcript	c.86G>A	p.Arg29His	missense_variant	1/2	1	NM_001304963.2	ENSP00000348831	P1
NUDT10	ENST00000376006.7 linkuse as main transcript	c.86G>A	p.Arg29His	missense_variant	2/3	1		ENSP00000365174	P1
	ENST00000425150.2 linkuse as main transcript	n.631-3486C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000260

AC:

AN:

111656

Hom.:

Cov.:

AF XY:

0.000207

AC XY:

AN XY:

33842

show subpopulations

Gnomad AFR

AF:

0.000911

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000941

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000835

AC:

AN:

179559

Hom.:

AF XY:

0.0000155

AC XY:

AN XY:

64651

show subpopulations

Gnomad AFR exome

AF:

0.00110

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000125

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000447

AC:

AN:

1097102

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

362616

show subpopulations

Gnomad4 AFR exome

AF:

0.00144

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000475

Gnomad4 OTH exome

AF:

0.000152

GnomAD4 genome

AF:

0.000260

AC:

AN:

111711

Hom.:

Cov.:

AF XY:

0.000206

AC XY:

AN XY:

33907

show subpopulations

Gnomad4 AFR

AF:

0.000909

Gnomad4 AMR

AF:

0.0000940

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000476

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 12, 2023

The c.86G>A (p.R29H) alteration is located in exon 2 (coding exon 1) of the NUDT10 gene. This alteration results from a G to A substitution at nucleotide position 86, causing the arginine (R) at amino acid position 29 to be replaced by a histidine (H). 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

0.086

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.049

T;T

FATHMM_MKL

Benign

0.10

LIST_S2

Uncertain

0.91

.;D

M_CAP

Benign

0.025

MetaRNN

Benign

0.0097

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;L

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.035

Sift

Benign

0.10

T;T

Sift4G

Benign

0.11

T;T

Polyphen

0.27

B;B

Vest4

0.24

MVP

0.28

ClinPred

0.030

GERP RS

0.77

Varity_R

0.14

gMVP

0.32

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over