Genetic Variant NADK:p.Glu444_Glu445dup (chr1-1752908-C-CCCTCCT) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP3BS1BS2

The NM_023018.5(NADK):c.1331_1336dupAGGAGG(p.Glu444_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 0.00398 in 1,525,748 control chromosomes in the GnomAD database, including 13 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0044 ( 2 hom., cov: 0)

Exomes 𝑓: 0.0039 ( 11 hom. )

Consequence

NADK
NM_023018.5 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_023018.5

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0044 (660/149940) while in subpopulation SAS AF = 0.0232 (109/4692). AF 95% confidence interval is 0.0197. There are 2 homozygotes in GnomAd4. There are 344 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NADK	NM_023018.5 link	c.1331_1336dupAGGAGG	p.Glu444_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.1331_1336dupAGGAGG	p.Glu444_Glu445dup	conservative_inframe_insertion	Exon 12 of 12	2	NM_023018.5	ENSP00000341679.5		O95544-1

Frequencies

GnomAD3 genomes

AF:

0.00443

AC:

663

AN:

149830

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00423

Gnomad AMI

AF:

0.0111

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00116

Gnomad EAS

AF:

0.00416

Gnomad SAS

AF:

0.0234

Gnomad FIN

AF:

0.000587

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.00378

Gnomad OTH

AF:

0.0112

GnomAD2 exomes

AF:

0.00552

AC:

899

AN:

162868

AF XY:

0.00621

show subpopulations

Gnomad AFR exome

AF:

0.00312

Gnomad AMR exome

AF:

0.00479

Gnomad ASJ exome

AF:

0.00166

Gnomad EAS exome

AF:

0.00570

Gnomad FIN exome

AF:

0.000195

Gnomad NFE exome

AF:

0.00240

Gnomad OTH exome

AF:

0.00648

GnomAD4 exome

AF:

0.00393

AC:

5411

AN:

1375808

Hom.:

Cov.:

AF XY:

0.00442

AC XY:

3019

AN XY:

682320

show subpopulations

African (AFR)

AF:

0.00397

AC:

130

AN:

32714

American (AMR)

AF:

0.00423

AC:

155

AN:

36648

Ashkenazi Jewish (ASJ)

AF:

0.00153

AC:

AN:

24796

East Asian (EAS)

AF:

0.00256

AC:

AN:

37176

South Asian (SAS)

AF:

0.0211

AC:

1716

AN:

81210

European-Finnish (FIN)

AF:

0.000349

AC:

AN:

48668

Middle Eastern (MID)

AF:

0.0130

AC:

AN:

5610

European-Non Finnish (NFE)

AF:

0.00277

AC:

2913

AN:

1051898

Other (OTH)

AF:

0.00480

AC:

274

AN:

57088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

298

596

894

1192

1490

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00440

AC:

660

AN:

149940

Hom.:

Cov.:

AF XY:

0.00471

AC XY:

344

AN XY:

73090

show subpopulations

African (AFR)

AF:

0.00422

AC:

173

AN:

41038

American (AMR)

AF:

0.00373

AC:

AN:

15022

Ashkenazi Jewish (ASJ)

AF:

0.00116

AC:

AN:

3454

East Asian (EAS)

AF:

0.00417

AC:

AN:

5030

South Asian (SAS)

AF:

0.0232

AC:

109

AN:

4692

European-Finnish (FIN)

AF:

0.000587

AC:

AN:

10216

Middle Eastern (MID)

AF:

0.0171

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00378

AC:

254

AN:

67230

Other (OTH)

AF:

0.0107

AC:

AN:

2064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

129

161

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00435

Hom.:

868

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.32

Mutation Taster

=73/27

polymorphism

(source)

Splicing

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

Publications

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1-1752908-CCCTCCTCCTCCTCCTCCT-CCCTCCTCCTCCTCCTCCTCCTCCT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over