X-51332990-C-G

Variant names:

• chrX-51332990-C-G
• rs1922718986
• NM_001304963.2:c.25C>G

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM1 PM2 PP3

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.393
• Publications: 0 publications found

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]

LINC01284 (HGNC:50342): (long intergenic non-protein coding RNA 1284)

LOC105373204 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304963.2. 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
	NUDT10	NM_001304963.2	MANE Select	c.25C>G	p.Arg9Gly	missense	Exon 1 of 2	NP_001291892.1	Q8NFP7
	NUDT10	NM_153183.4		c.25C>G	p.Arg9Gly	missense	Exon 2 of 3	NP_694853.1	Q8NFP7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDT10	ENST00000356450.3	TSL:1 MANE Select	c.25C>G	p.Arg9Gly	missense	Exon 1 of 2	ENSP00000348831.2	Q8NFP7
	NUDT10	ENST00000376006.7	TSL:1	c.25C>G	p.Arg9Gly	missense	Exon 2 of 3	ENSP00000365174.3	Q8NFP7
	LINC01284	ENST00000425150.2	TSL:3	n.631-3425G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000895 AC: 1 AN: 111716 Hom.: 0 Cov.: 23

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: 13 AN: 1097915 Hom.: 0 Cov.: 36 AF XY: 0.00000275 AC XY: 1 AN XY: 363423

African (AFR) AF: 0.00 AC: 0 AN: 26397

American (AMR) AF: 0.00 AC: 0 AN: 35195

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19365

East Asian (EAS) AF: 0.00 AC: 0 AN: 30196

South Asian (SAS) AF: 0.00 AC: 0 AN: 54099

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40517

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.0000119 AC: 10 AN: 841926

Other (OTH) AF: 0.0000651 AC: 3 AN: 46083

GnomAD4 genome AF: 0.00000895 AC: 1 AN: 111716 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33894

African (AFR) AF: 0.00 AC: 0 AN: 30772

American (AMR) AF: 0.00 AC: 0 AN: 10596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 3501

South Asian (SAS) AF: 0.00 AC: 0 AN: 2635

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6037

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53114

Other (OTH) AF: 0.00 AC: 0 AN: 1494

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
FATHMM_MKL	Benign	0.33	N
LIST_S2	Uncertain	0.96	D
M_CAP	Pathogenic	0.61	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-0.39	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.39
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.67
MutPred		0.44		Gain of helix (P = 0.0349)
MVP		0.25
ClinPred		0.99	D
GERP RS		2.6
PromoterAI		-0.054	Neutral
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

Other links and lift over

dbSNP: rs1922718986; hg19: chrX-51075842;