Genetic Variant NADK:p.Glu443_Glu445del (chr1-1752908-CCCTCCTCCT-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3

The NM_023018.5(NADK):c.1328_1336delAGGAGGAGG(p.Glu443_Glu445del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000518 in 1,526,018 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

NADK
NM_023018.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.426

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: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP3

Nonframeshift variant in repetitive region in NM_023018.5

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023018.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NADK	NM_023018.5	MANE Select	c.1328_1336delAGGAGGAGG	p.Glu443_Glu445del	disruptive_inframe_deletion	Exon 12 of 12	NP_075394.3
NADK	NM_001198994.2		c.1763_1771delAGGAGGAGG	p.Glu588_Glu590del	disruptive_inframe_deletion	Exon 14 of 14	NP_001185923.1	O95544-2
NADK	NM_001198993.2		c.1328_1336delAGGAGGAGG	p.Glu443_Glu445del	disruptive_inframe_deletion	Exon 12 of 12	NP_001185922.1	O95544-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NADK	ENST00000341426.9	TSL:2 MANE Select	c.1328_1336delAGGAGGAGG	p.Glu443_Glu445del	disruptive_inframe_deletion	Exon 12 of 12	ENSP00000341679.5	O95544-1
NADK	ENST00000378625.5	TSL:1	c.1763_1771delAGGAGGAGG	p.Glu588_Glu590del	disruptive_inframe_deletion	Exon 14 of 14	ENSP00000367890.1	O95544-2
NADK	ENST00000341991.7	TSL:1	c.1328_1336delAGGAGGAGG	p.Glu443_Glu445del	disruptive_inframe_deletion	Exon 12 of 12	ENSP00000344340.3	O95544-1

Frequencies

GnomAD3 genomes

AF:

0.0000734

AC:

AN:

149844

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000666

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000198

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000595

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000860

AC:

AN:

162868

AF XY:

0.0000458

show subpopulations

Gnomad AFR exome

AF:

0.0000974

Gnomad AMR exome

AF:

0.000212

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000650

Gnomad NFE exome

AF:

0.0000995

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000494

AC:

AN:

1376174

Hom.:

AF XY:

0.0000630

AC XY:

AN XY:

682494

show subpopulations

African (AFR)

AF:

0.000122

AC:

AN:

32714

American (AMR)

AF:

0.000109

AC:

AN:

36650

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24798

East Asian (EAS)

AF:

0.00

AC:

AN:

37178

South Asian (SAS)

AF:

0.0000369

AC:

AN:

81228

European-Finnish (FIN)

AF:

0.0000205

AC:

AN:

48670

Middle Eastern (MID)

AF:

0.000178

AC:

AN:

5610

European-Non Finnish (NFE)

AF:

0.0000504

AC:

AN:

1052228

Other (OTH)

AF:

0.0000350

AC:

AN:

57098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000734

AC:

AN:

149844

Hom.:

Cov.:

AF XY:

0.0000685

AC XY:

AN XY:

72972

show subpopulations

African (AFR)

AF:

0.000122

AC:

AN:

40922

American (AMR)

AF:

0.0000666

AC:

AN:

15004

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3454

East Asian (EAS)

AF:

0.000198

AC:

AN:

5044

South Asian (SAS)

AF:

0.00

AC:

AN:

4698

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10218

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000595

AC:

AN:

67242

Other (OTH)

AF:

0.00

AC:

AN:

2046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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:

0.00

Hom.:

868

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.43

Mutation Taster

=104/96

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

1-1752908-CCCTCCTCCTCCTCCTCCT-CCCTCCTCCT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over