X-51333119-A-G

Position:

chrX-51333119-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000356450.3(NUDT10):c.154A>G(p.Met52Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000898 in 111,395 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M52L) has been classified as Uncertain significance.

Frequency

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

Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )

Failed GnomAD Quality Control

Consequence

NUDT10
ENST00000356450.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.54

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09038448).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUDT10	NM_001304963.2 linkuse as main transcript	c.154A>G	p.Met52Val	missense_variant	1/2	ENST00000356450.3	NP_001291892.1
LOC105373204	XR_007068239.1 linkuse as main transcript	n.732-3554T>C		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.154A>G	p.Met52Val	missense_variant	1/2	1	NM_001304963.2	ENSP00000348831	P1
NUDT10	ENST00000376006.7 linkuse as main transcript	c.154A>G	p.Met52Val	missense_variant	2/3	1		ENSP00000365174	P1
	ENST00000425150.2 linkuse as main transcript	n.631-3554T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00000898

AC:

AN:

111395

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33581

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:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000567

AC:

AN:

176413

Hom.:

AF XY:

0.0000159

AC XY:

AN XY:

63055

show subpopulations

Gnomad AFR exome

AF:

0.0000826

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000182

AC:

AN:

1096923

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

362523

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

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:

0.00000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000898

AC:

AN:

111395

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33581

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:

0.0000189

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Sep 27, 2021

The c.154A>G (p.M52V) alteration is located in exon 2 (coding exon 1) of the NUDT10 gene. This alteration results from a A to G substitution at nucleotide position 154, causing the methionine (M) at amino acid position 52 to be replaced by a valine (V). 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

0.11

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.042

T;T

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.87

.;D

M_CAP

Benign

0.0092

MetaRNN

Benign

0.090

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.84

N;N

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.21

Sift

Benign

0.45

T;T

Sift4G

Benign

0.62

T;T

Polyphen

0.0

B;B

Vest4

0.48

MutPred

0.26

Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);

MVP

0.44

ClinPred

0.025

GERP RS

-1.5

Varity_R

0.50

gMVP

0.49

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