10-73125154-T-G

Variant names:

• chr10-73125154-T-G
• rs768344112
• NM_015901.6:c.502T>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_015901.6(NUDT13):​c.502T>G​(p.Phe168Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F168L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NUDT13 NM_015901.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.47
• Publications: 0 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.91

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.502T>G	p.Phe168Val	missense	Exon 6 of 9	NP_056985.3
	NUDT13	NM_001283014.2		c.502T>G	p.Phe168Val	missense	Exon 6 of 7	NP_001269943.1	Q86X67-2
	NUDT13	NM_001283015.2		c.502T>G	p.Phe168Val	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.502T>G	p.Phe168Val	missense	Exon 6 of 9	ENSP00000349874.4	Q86X67-1
	NUDT13	ENST00000349051.9	TSL:1	c.502T>G	p.Phe168Val	missense	Exon 6 of 7	ENSP00000335326.6	Q86X67-2
	NUDT13	ENST00000372997.3	TSL:1	c.502T>G	p.Phe168Val	missense	Exon 6 of 8	ENSP00000362088.3	Q86X67-4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461230 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726988

African (AFR) AF: 0.00 AC: 0 AN: 33420

American (AMR) AF: 0.00 AC: 0 AN: 44430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111838

Other (OTH) AF: 0.00 AC: 0 AN: 60348

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T
Eigen	Pathogenic	0.90
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Uncertain	0.21	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.5
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Pathogenic	0.74
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.99	D
Vest4		0.85
MutPred		0.75		Gain of MoRF binding (P = 0.0694)
MVP		0.85
MPC		0.38
ClinPred		0.99	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.80
gMVP		0.79
Mutation Taster		=149/151	disease causing

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

Other links and lift over

dbSNP: rs768344112; hg19: chr10-74884912;