X-51332990-C-G

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP3

The NM_001304963.2(NUDT10):c.25C>G(p.Arg9Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,209,631 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000012 ( 0 hom. 1 hem. )

Consequence

NUDT10
NM_001304963.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.393

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:

ENSG00000229151 (HGNC:):

ENSG00000229151 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM1

In a binding_site (size 0) in uniprot entity NUD10_HUMAN

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.805

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUDT10	NM_001304963.2 link	c.25C>G	p.Arg9Gly	missense_variant	Exon 1 of 2	ENST00000356450.3	NP_001291892.1	Q8NFP7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NUDT10	ENST00000356450.3 link	c.25C>G	p.Arg9Gly	missense_variant	Exon 1 of 2	1	NM_001304963.2	ENSP00000348831.2	Q8NFP7
NUDT10	ENST00000376006.7 link	c.25C>G	p.Arg9Gly	missense_variant	Exon 2 of 3	1		ENSP00000365174.3	Q8NFP7
ENSG00000229151	ENST00000425150.2 link	n.631-3425G>C		intron_variant	Intron 4 of 8	3

Frequencies

GnomAD3 genomes

AF:

0.00000895

AC:

AN:

111716

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33894

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000118

AC:

AN:

1097915

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363423

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000119

Gnomad4 OTH exome

AF:

0.0000651

GnomAD4 genome

AF:

0.00000895

AC:

AN:

111716

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33894

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 25, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.25C>G (p.R9G) alteration is located in exon 2 (coding exon 1) of the NUDT10 gene. This alteration results from a C to G substitution at nucleotide position 25, causing the arginine (R) at amino acid position 9 to be replaced by a glycine (G). 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

Pathogenic

0.98

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;T

FATHMM_MKL

Benign

0.33

LIST_S2

Uncertain

0.96

.;D

M_CAP

Pathogenic

0.61

MetaRNN

Pathogenic

0.80

D;D

MetaSVM

Benign

-0.39

MutationAssessor

Uncertain

2.7

M;M

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-5.3

D;D

REVEL

Uncertain

0.39

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

1.0

D;D

Vest4

0.67

MutPred

0.44

Gain of helix (P = 0.0349);Gain of helix (P = 0.0349);

MVP

0.25

ClinPred

0.99

GERP RS

2.6

Varity_R

0.88

gMVP

0.77

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

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