chr10-73122189-C-G

Variant names:

• chr10-73122189-C-G
• NM_015901.6:c.238C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015901.6(NUDT13):​c.238C>G​(p.Leu80Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,460,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: NUDT13 NM_015901.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.48
• 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]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2902034).

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.238C>G	p.Leu80Val	missense	Exon 4 of 9	NP_056985.3
	NUDT13	NM_001283014.2		c.238C>G	p.Leu80Val	missense	Exon 4 of 7	NP_001269943.1	Q86X67-2
	NUDT13	NM_001283015.2		c.238C>G	p.Leu80Val	missense	Exon 4 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.238C>G	p.Leu80Val	missense	Exon 4 of 9	ENSP00000349874.4	Q86X67-1
	NUDT13	ENST00000349051.9	TSL:1	c.238C>G	p.Leu80Val	missense	Exon 4 of 7	ENSP00000335326.6	Q86X67-2
	NUDT13	ENST00000372997.3	TSL:1	c.238C>G	p.Leu80Val	missense	Exon 4 of 8	ENSP00000362088.3	Q86X67-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000130 AC: 19 AN: 1460586 Hom.: 0 Cov.: 30 AF XY: 0.0000179 AC XY: 13 AN XY: 726564

African (AFR) AF: 0.00 AC: 0 AN: 33414

American (AMR) AF: 0.00 AC: 0 AN: 44324

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 85926

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1111672

Other (OTH) AF: 0.0000166 AC: 1 AN: 60352

GnomAD4 genome Cov.: 32

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	Benign	0.14
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0065	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.54	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		1.5
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.27
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.040	D
Polyphen		1.0	D
Vest4		0.43
MutPred		0.49		Gain of sheet (P = 0.0061)
MVP		0.49
MPC		0.40
ClinPred		0.92	D
GERP RS		4.1
Varity_R		0.28
gMVP		0.62
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr10-74881947;