1-1752908-CCCTCCTCCTCCTCCTCCT-CCCTCCTCCT

Variant names:

• chr1-1752908-CCCTCCTCCT-C
• rs71578334
• NM_023018.5:c.1328_1336delAGGAGGAGG

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP3

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.426
• Publications: 4 publications found

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]

ACMG classification

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NADK	NM_023018.5	c.1328_1336delAGGAGGAGG	p.Glu443_Glu445del	disruptive_inframe_deletion	Exon 12 of 12	ENST00000341426.9	NP_075394.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NADK	ENST00000341426.9	c.1328_1336delAGGAGGAGG	p.Glu443_Glu445del	disruptive_inframe_deletion	Exon 12 of 12	2	NM_023018.5	ENSP00000341679.5

Frequencies

GnomAD3 genomes AF: 0.0000734 AC: 11 AN: 149844 Hom.: 0 Cov.: 0

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: 14 AN: 162868 AF XY: 0.0000458

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: 68 AN: 1376174 Hom.: 0 AF XY: 0.0000630 AC XY: 43 AN XY: 682494

African (AFR) AF: 0.000122 AC: 4 AN: 32714

American (AMR) AF: 0.000109 AC: 4 AN: 36650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24798

East Asian (EAS) AF: 0.00 AC: 0 AN: 37178

South Asian (SAS) AF: 0.0000369 AC: 3 AN: 81228

European-Finnish (FIN) AF: 0.0000205 AC: 1 AN: 48670

Middle Eastern (MID) AF: 0.000178 AC: 1 AN: 5610

European-Non Finnish (NFE) AF: 0.0000504 AC: 53 AN: 1052228

Other (OTH) AF: 0.0000350 AC: 2 AN: 57098

GnomAD4 genome AF: 0.0000734 AC: 11 AN: 149844 Hom.: 0 Cov.: 0 AF XY: 0.0000685 AC XY: 5 AN XY: 72972

African (AFR) AF: 0.000122 AC: 5 AN: 40922

American (AMR) AF: 0.0000666 AC: 1 AN: 15004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.000198 AC: 1 AN: 5044

South Asian (SAS) AF: 0.00 AC: 0 AN: 4698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10218

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

European-Non Finnish (NFE) AF: 0.0000595 AC: 4 AN: 67242

Other (OTH) AF: 0.00 AC: 0 AN: 2046

Alfa AF: 0.00 Hom.: 868

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.43
Mutation Taster		=104/96	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs71578334; hg19: chr1-1684347;