1-1752908-CCCTCCTCCTCCTCCTCCT-CCCTCCTCCTCCTCCTCCTCCTCCTCCT

Variant names:

• chr1-1752908-C-CCCTCCTCCT
• rs71578334
• NM_023018.5:c.1328_1336dupAGGAGGAGG

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_023018.5(NADK):​c.1328_1336dupAGGAGGAGG​(p.Glu443_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 0.000311 in 1,526,094 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 0.00018 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00032 (0 hom.)
• Consequence: NADK NM_023018.5 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.315
• 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: Likely_benign. The variant received -1 ACMG points.

• 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_1336dupAGGAGGAGG	p.Glu443_Glu445dup	conservative_inframe_insertion	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_1336dupAGGAGGAGG	p.Glu443_Glu445dup	conservative_inframe_insertion	Exon 12 of 12	2	NM_023018.5	ENSP00000341679.5

Frequencies

GnomAD3 genomes AF: 0.000180 AC: 27 AN: 149842 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000238

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000135 AC: 22 AN: 162868 AF XY: 0.000138

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000170

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000325 AC: 447 AN: 1376142 Hom.: 0 Cov.: 39 AF XY: 0.000330 AC XY: 225 AN XY: 682480

African (AFR) AF: 0.000306 AC: 10 AN: 32716

American (AMR) AF: 0.000164 AC: 6 AN: 36650

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

East Asian (EAS) AF: 0.0000269 AC: 1 AN: 37178

South Asian (SAS) AF: 0.000222 AC: 18 AN: 81226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48670

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5610

European-Non Finnish (NFE) AF: 0.000377 AC: 397 AN: 1052198

Other (OTH) AF: 0.000263 AC: 15 AN: 57096

GnomAD4 genome AF: 0.000180 AC: 27 AN: 149952 Hom.: 0 Cov.: 0 AF XY: 0.000178 AC XY: 13 AN XY: 73096

African (AFR) AF: 0.000244 AC: 10 AN: 41044

American (AMR) AF: 0.00 AC: 0 AN: 15024

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

East Asian (EAS) AF: 0.000199 AC: 1 AN: 5030

South Asian (SAS) AF: 0.00 AC: 0 AN: 4692

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000238 AC: 16 AN: 67234

Other (OTH) AF: 0.00 AC: 0 AN: 2064

Alfa AF: 0.00 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

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;