Genetic Variant NADK:p.Glu445dup (chr1-1752908-C-CCCT) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP3BP6_ModerateBA1

The NM_023018.5(NADK):c.1334_1336dupAGG(p.Glu445dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 1,525,002 control chromosomes in the GnomAD database, including 80,559 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.39 ( 13066 hom., cov: 0)

Exomes 𝑓: 0.40 ( 67493 hom. )

Consequence

NADK
NM_023018.5 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.315

Publications

4 publications found

Variant links:

Genes affected

NADK (HGNC:29831): (NAD kinase) NADK catalyzes the transfer of a phosphate group from ATP to NAD to generate NADP, which in its reduced form acts as an electron donor for biosynthetic reactions (Lerner et al., 2001 [PubMed 11594753]).[supplied by OMIM, Mar 2008]

NADK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_023018.5

BP6

Variant 1-1752908-C-CCCT is Benign according to our data. Variant chr1-1752908-C-CCCT is described in ClinVar as [Benign]. Clinvar id is 2672290.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NADK	NM_023018.5 link	c.1334_1336dupAGG	p.Glu445dup	conservative_inframe_insertion	Exon 12 of 12	ENST00000341426.9	NP_075394.3	O95544-1A0A024R058

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NADK	ENST00000341426.9 link	c.1334_1336dupAGG	p.Glu445dup	conservative_inframe_insertion	Exon 12 of 12	2	NM_023018.5	ENSP00000341679.5		O95544-1

Frequencies

GnomAD3 genomes

AF:

0.392

AC:

58747

AN:

149740

Hom.:

13051

Cov.:

show subpopulations

Gnomad AFR

AF:

0.168

Gnomad AMI

AF:

0.551

Gnomad AMR

AF:

0.534

Gnomad ASJ

AF:

0.383

Gnomad EAS

AF:

0.373

Gnomad SAS

AF:

0.315

Gnomad FIN

AF:

0.475

Gnomad MID

AF:

0.363

Gnomad NFE

AF:

0.490

Gnomad OTH

AF:

0.407

GnomAD2 exomes

AF:

0.374

AC:

60843

AN:

162868

AF XY:

0.370

show subpopulations

Gnomad AFR exome

AF:

0.145

Gnomad AMR exome

AF:

0.461

Gnomad ASJ exome

AF:

0.360

Gnomad EAS exome

AF:

0.329

Gnomad FIN exome

AF:

0.418

Gnomad NFE exome

AF:

0.392

Gnomad OTH exome

AF:

0.397

GnomAD4 exome

AF:

0.395

AC:

543656

AN:

1375152

Hom.:

67493

Cov.:

AF XY:

0.390

AC XY:

265653

AN XY:

681934

show subpopulations

African (AFR)

AF:

0.146

AC:

4779

AN:

32700

American (AMR)

AF:

0.437

AC:

15991

AN:

36614

Ashkenazi Jewish (ASJ)

AF:

0.327

AC:

8085

AN:

24760

East Asian (EAS)

AF:

0.319

AC:

11864

AN:

37160

South Asian (SAS)

AF:

0.270

AC:

21904

AN:

81106

European-Finnish (FIN)

AF:

0.410

AC:

19923

AN:

48632

Middle Eastern (MID)

AF:

0.288

AC:

1612

AN:

5606

European-Non Finnish (NFE)

AF:

0.417

AC:

438018

AN:

1051538

Other (OTH)

AF:

0.377

AC:

21480

AN:

57036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

18508

37016

55523

74031

92539

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.392

AC:

58785

AN:

149850

Hom.:

13066

Cov.:

AF XY:

0.390

AC XY:

28486

AN XY:

73048

show subpopulations

African (AFR)

AF:

0.167

AC:

6868

AN:

41022

American (AMR)

AF:

0.535

AC:

8031

AN:

15012

Ashkenazi Jewish (ASJ)

AF:

0.383

AC:

1323

AN:

3454

East Asian (EAS)

AF:

0.373

AC:

1875

AN:

5026

South Asian (SAS)

AF:

0.316

AC:

1483

AN:

4690

European-Finnish (FIN)

AF:

0.475

AC:

4844

AN:

10202

Middle Eastern (MID)

AF:

0.360

AC:

105

AN:

292

European-Non Finnish (NFE)

AF:

0.490

AC:

32915

AN:

67190

Other (OTH)

AF:

0.410

AC:

845

AN:

2062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1557

3114

4672

6229

7786

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.278

Hom.:

868

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Dec 12, 2023

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.32

Mutation Taster

=73/27

polymorphism (auto)

(source)

Splicing

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

Publications

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chr1-1752908-C-CCCT

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