chr10-73120040-G-T

Position:

• chr10-73120040-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015901.6(NUDT13):​c.106G>T​(p.Asp36Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NUDT13 NM_015901.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.42

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUDT13	NM_015901.6	c.106G>T	p.Asp36Tyr	missense_variant	3/9	ENST00000357321.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUDT13	ENST00000357321.9	c.106G>T	p.Asp36Tyr	missense_variant	3/9	5	NM_015901.6	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Feb 17, 2024

The c.106G>T (p.D36Y) alteration is located in exon 3 (coding exon 2) of the NUDT13 gene. This alteration results from a G to T substitution at nucleotide position 106, causing the aspartic acid (D) at amino acid position 36 to be replaced by a tyrosine (Y). 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	0.20
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	.;T;.;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.58	D;D;D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.2	.;M;M;M
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-4.8	.;D;D;D
REVEL	Uncertain	0.29
Sift	Uncertain	0.0020	.;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D
Polyphen		1.0	.;D;D;.
Vest4		0.65
MutPred		0.46		Loss of disorder (P = 0.014);Loss of disorder (P = 0.014);Loss of disorder (P = 0.014);Loss of disorder (P = 0.014);
MVP		0.67
MPC		0.43
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.70
gMVP		0.89

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

Publications

LitVar

Other links and lift over

dbSNP: rs1385230228; hg19: chr10-74879798;