10-73122189-C-G

Position:

• chr10-73122189-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/21 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

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUDT13	NM_015901.6	c.238C>G	p.Leu80Val	missense_variant	4/9	ENST00000357321.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUDT13	ENST00000357321.9	c.238C>G	p.Leu80Val	missense_variant	4/9	5	NM_015901.6	P1

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

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: 0.0000187

Gnomad4 NFE exome AF: 0.0000153

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

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

Aug 16, 2021

The c.238C>G (p.L80V) alteration is located in exon 4 (coding exon 3) of the NUDT13 gene. This alteration results from a C to G substitution at nucleotide position 238, causing the leucine (L) at amino acid position 80 to be replaced by a valine (V). 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	Benign	0.14
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Uncertain	1.0
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D;D;D;D
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.29	T;T;T;T
MetaSVM	Benign	-0.54	T
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Benign	0.37	T
Sift4G	Uncertain	0.040	D;T;D;D
Polyphen		1.0, 1.0	.;D;D;.
Vest4		0.43
MutPred		0.49		Gain of sheet (P = 0.0061);Gain of sheet (P = 0.0061);Gain of sheet (P = 0.0061);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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-74881947;