10-73114447-C-T

Variant names:

• chr10-73114447-C-T
• rs199672264
• NM_015901.6:c.82C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001283016.2(NUDT13):​c.-369C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000391 in 1,561,286 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: NUDT13 NM_001283016.2 5_prime_UTR_premature_start_codon_gain
• Scores: Splicing: ADA: 0.0002940
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.861
• 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 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001283016.2. 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.82C>T	p.Arg28Trp	missense splice_region	Exon 2 of 9	NP_056985.3
	NUDT13	NM_001283016.2		c.-369C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 10	NP_001269945.1	Q86X67-3
	NUDT13	NM_001283017.2		c.-475C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 9	NP_001269946.1	B4E059

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDT13	ENST00000357321.9	TSL:5 MANE Select	c.82C>T	p.Arg28Trp	missense splice_region	Exon 2 of 9	ENSP00000349874.4	Q86X67-1
	NUDT13	ENST00000349051.9	TSL:1	c.82C>T	p.Arg28Trp	missense splice_region	Exon 2 of 7	ENSP00000335326.6	Q86X67-2
	NUDT13	ENST00000372997.3	TSL:1	c.82C>T	p.Arg28Trp	missense splice_region	Exon 2 of 8	ENSP00000362088.3	Q86X67-4

Frequencies

GnomAD3 genomes AF: 0.0000266 AC: 4 AN: 150610 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000123 AC: 3 AN: 243674 AF XY: 0.0000152

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000569

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000901

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000404 AC: 57 AN: 1410676 Hom.: 0 Cov.: 26 AF XY: 0.0000385 AC XY: 27 AN XY: 701458

African (AFR) AF: 0.0000307 AC: 1 AN: 32604

American (AMR) AF: 0.00 AC: 0 AN: 43154

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24928

East Asian (EAS) AF: 0.0000256 AC: 1 AN: 39036

South Asian (SAS) AF: 0.0000390 AC: 3 AN: 76894

European-Finnish (FIN) AF: 0.0000195 AC: 1 AN: 51176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5562

European-Non Finnish (NFE) AF: 0.0000463 AC: 50 AN: 1079404

Other (OTH) AF: 0.0000173 AC: 1 AN: 57918

GnomAD4 genome AF: 0.0000266 AC: 4 AN: 150610 Hom.: 0 Cov.: 31 AF XY: 0.0000409 AC XY: 3 AN XY: 73422

African (AFR) AF: 0.0000244 AC: 1 AN: 40968

American (AMR) AF: 0.00 AC: 0 AN: 15028

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10040

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67860

Other (OTH) AF: 0.00 AC: 0 AN: 2066

Alfa AF: 0.0000170 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.00000824 AC: 1

Asia WGS AF: 0.000578 AC: 2 AN: 3472

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	0.26
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Benign	0.18
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.54	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.86
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.74
MVP		0.72
MPC		0.40
ClinPred		0.97	D
GERP RS		2.1
Varity_R		0.43
gMVP		0.78
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00029
dbscSNV1_RF	Benign	0.14
SpliceAI score (max)		0.11		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: rs199672264; hg19: chr10-74874205;