X-51333239-A-G

Position:

• chrX-51333239-A-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3 BS2

The NM_001304963.2(NUDT10):​c.274A>G​(p.Arg92Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000911 in 1,098,091 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0000091 (0 hom. 5 hem.)
• Consequence: NUDT10 NM_001304963.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.527

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]

ENSG00000229151 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.794
• BS2: High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUDT10	NM_001304963.2	c.274A>G	p.Arg92Gly	missense_variant	1/2	ENST00000356450.3	NP_001291892.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUDT10	ENST00000356450.3	c.274A>G	p.Arg92Gly	missense_variant	1/2	1	NM_001304963.2	ENSP00000348831.2
NUDT10	ENST00000376006.7	c.274A>G	p.Arg92Gly	missense_variant	2/3	1		ENSP00000365174.3
ENSG00000229151	ENST00000425150.2	n.631-3674T>C		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 0.00000911 AC: 10 AN: 1098091 Hom.: 0 Cov.: 33 AF XY: 0.0000138 AC XY: 5 AN XY: 363563

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: 0.00

GnomAD4 genome Cov.: 21

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 13, 2022

The c.274A>G (p.R92G) 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 274, causing the arginine (R) at amino acid position 92 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	0.99
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;T
FATHMM_MKL	Benign	0.18	N
LIST_S2	Uncertain	0.97	.;D
M_CAP	Benign	0.037	D
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M;M
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-6.6	D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0010	D;D
Sift4G	Benign	0.061	T;T
Polyphen		1.0	D;D
Vest4		0.85
MutPred		0.71		Loss of glycosylation at P89 (P = 0.0731);Loss of glycosylation at P89 (P = 0.0731);
MVP		0.16
ClinPred		0.99	D
GERP RS		-2.3
Varity_R		0.97
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-51076091;