NM_015901.6:c.527C>T

Variant names:

• chr10-73125179-C-T
• rs202052984
• NM_015901.6:c.527C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_015901.6(NUDT13):​c.527C>T​(p.Thr176Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000843 in 1,613,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. T176P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000086 (0 hom.)
• Consequence: NUDT13 NM_015901.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.66
• Publications: 3 publications found

Genes affected

NUDT13 (HGNC:18827): (nudix hydrolase 13) Predicted to enable NADH pyrophosphatase activity. Predicted to be involved in NADH metabolic process and NADP catabolic process. Predicted to be located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000272599 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.83

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015901.6. 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
	NUDT13	NM_015901.6	MANE Select	c.527C>T	p.Thr176Ile	missense	Exon 6 of 9	NP_056985.3
	NUDT13	NM_001283014.2		c.527C>T	p.Thr176Ile	missense	Exon 6 of 7	NP_001269943.1	Q86X67-2
	NUDT13	NM_001283015.2		c.527C>T	p.Thr176Ile	missense	Exon 6 of 8	NP_001269944.1	Q86X67-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDT13	ENST00000357321.9	TSL:5 MANE Select	c.527C>T	p.Thr176Ile	missense	Exon 6 of 9	ENSP00000349874.4	Q86X67-1
	NUDT13	ENST00000349051.9	TSL:1	c.527C>T	p.Thr176Ile	missense	Exon 6 of 7	ENSP00000335326.6	Q86X67-2
	NUDT13	ENST00000372997.3	TSL:1	c.527C>T	p.Thr176Ile	missense	Exon 6 of 8	ENSP00000362088.3	Q86X67-4

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152084 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000121

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: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 250822 AF XY: 0.0000369

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000529

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000855 AC: 125 AN: 1461492 Hom.: 0 Cov.: 31 AF XY: 0.0000866 AC XY: 63 AN XY: 727070

African (AFR) AF: 0.000479 AC: 16 AN: 33418

American (AMR) AF: 0.00 AC: 0 AN: 44558

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5762

European-Non Finnish (NFE) AF: 0.0000899 AC: 100 AN: 1111920

Other (OTH) AF: 0.000133 AC: 8 AN: 60358

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152084 Hom.: 0 Cov.: 31 AF XY: 0.000121 AC XY: 9 AN XY: 74284

African (AFR) AF: 0.000121 AC: 5 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000745 Hom.: 1

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ExAC AF: 0.0000165 AC: 2

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	0.68
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.073	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Uncertain	-0.034	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.7
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Uncertain	0.51
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.69	P
Vest4		0.88
MutPred		0.58		Loss of phosphorylation at T176 (P = 0.0176)
MVP		0.65
MPC		0.37
ClinPred		0.95	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.73
gMVP		0.78
Mutation Taster		=179/121	polymorphism

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: rs202052984; hg19: chr10-74884937; COSMIC: COSV61970442; COSMIC: COSV61970442;