chr13-48037782-AGGAGTC-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 3P and 6B. PM4PP3BP6_ModerateBS2

The NM_018283.4(NUDT15):c.50_55delGAGTCG(p.Gly17_Val18del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 1,587,330 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 6 hom. )

Consequence

NUDT15
NM_018283.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 8.38

Publications

30 publications found

Variant links:

Genes affected

NUDT15 (HGNC:23063): (nudix hydrolase 15) This gene encodes an enzyme that belongs to the Nudix hydrolase superfamily. Members of this superfamily catalyze the hydrolysis of nucleoside diphosphates, including substrates like 8-oxo-dGTP, which are a result of oxidative damage, and can induce base mispairing during DNA replication, causing transversions. The encoded enzyme is a negative regulator of thiopurine activation and toxicity. Mutations in this gene result in poor metabolism of thiopurines, and are associated with thiopurine-induced early leukopenia. Multiple pseudogenes of this gene have been identified. [provided by RefSeq, Apr 2016]

NUDT15 links:

LOC124903172 (HGNC:):

LOC124903172 links:

SUCLA2 (HGNC:11448): (succinate-CoA ligase ADP-forming subunit beta) Succinyl-CoA synthetase (SCS) is a mitochondrial matrix enzyme that acts as a heterodimer, being composed of an invariant alpha subunit and a substrate-specific beta subunit. The protein encoded by this gene is an ATP-specific SCS beta subunit that dimerizes with the SCS alpha subunit to form SCS-A, an essential component of the tricarboxylic acid cycle. SCS-A hydrolyzes ATP to convert succinate to succinyl-CoA. Defects in this gene are a cause of myopathic mitochondrial DNA depletion syndrome. A pseudogene of this gene has been found on chromosome 6. [provided by RefSeq, Jul 2008]

SUCLA2 Gene-Disease associations (from GenCC):

Leigh syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria
Inheritance: Mitochondrial, AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

SUCLA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_018283.4.

PP3

No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

BP6

Variant 13-48037782-AGGAGTC-A is Benign according to our data. Variant chr13-48037782-AGGAGTC-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2643811.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 190 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUDT15	NM_018283.4 link	c.50_55delGAGTCG	p.Gly17_Val18del	disruptive_inframe_deletion	Exon 1 of 3	ENST00000258662.3	NP_060753.1	Q9NV35

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NUDT15	ENST00000258662.3 link	c.50_55delGAGTCG	p.Gly17_Val18del	disruptive_inframe_deletion	Exon 1 of 3	1	NM_018283.4	ENSP00000258662.1	Q9NV35
SUCLA2	ENST00000646804.1 link	c.-267_-262delGACTCC		5_prime_UTR_variant	Exon 1 of 11			ENSP00000493977.1	A0A2R8YDQ9
SUCLA2	ENST00000643246.1 link	c.-345_-340delGACTCC		5_prime_UTR_variant	Exon 1 of 3			ENSP00000496235.1	A0A2R8YF84

Frequencies

GnomAD3 genomes

AF:

0.00125

AC:

190

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00226

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.00103

AC:

209

AN:

202908

AF XY:

0.000971

show subpopulations

Gnomad AFR exome

AF:

0.000315

Gnomad AMR exome

AF:

0.000252

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000565

Gnomad NFE exome

AF:

0.00196

Gnomad OTH exome

AF:

0.000193

GnomAD4 exome

AF:

0.00172

AC:

2472

AN:

1435038

Hom.:

AF XY:

0.00173

AC XY:

1228

AN XY:

711128

show subpopulations

African (AFR)

AF:

0.000360

AC:

AN:

33322

American (AMR)

AF:

0.000387

AC:

AN:

38744

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25502

East Asian (EAS)

AF:

0.0000515

AC:

AN:

38812

South Asian (SAS)

AF:

0.000462

AC:

AN:

82228

European-Finnish (FIN)

AF:

0.000854

AC:

AN:

51518

Middle Eastern (MID)

AF:

0.000682

AC:

AN:

4402

European-Non Finnish (NFE)

AF:

0.00208

AC:

2287

AN:

1101052

Other (OTH)

AF:

0.00119

AC:

AN:

59458

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

132

264

396

528

660

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

288

384

480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00125

AC:

190

AN:

152292

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41572

American (AMR)

AF:

0.00105

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000471

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00226

AC:

154

AN:

68014

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000625

Hom.:

Bravo

AF:

0.00137

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

NUDT15: PM4, BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

8.4

Mutation Taster

=49/151

disease causing

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over