NM_023018.5:c.1334_1336dupAGG

Variant names:

• chr1-1752908-C-CCCT
• rs71578334
• NM_023018.5:c.1334_1336dupAGG

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: 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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NADK	NM_023018.5	MANE Select	c.1334_1336dupAGG	p.Glu445dup	conservative_inframe_insertion	Exon 12 of 12	NP_075394.3
	NADK	NM_001198994.2		c.1769_1771dupAGG	p.Glu590dup	conservative_inframe_insertion	Exon 14 of 14	NP_001185923.1	O95544-2
	NADK	NM_001198993.2		c.1334_1336dupAGG	p.Glu445dup	conservative_inframe_insertion	Exon 12 of 12	NP_001185922.1	O95544-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NADK	ENST00000341426.9	TSL:2 MANE Select	c.1334_1336dupAGG	p.Glu445dup	conservative_inframe_insertion	Exon 12 of 12	ENSP00000341679.5	O95544-1
	NADK	ENST00000378625.5	TSL:1	c.1769_1771dupAGG	p.Glu590dup	conservative_inframe_insertion	Exon 14 of 14	ENSP00000367890.1	O95544-2
	NADK	ENST00000341991.7	TSL:1	c.1334_1336dupAGG	p.Glu445dup	conservative_inframe_insertion	Exon 12 of 12	ENSP00000344340.3	O95544-1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 58747 AN: 149740 Hom.: 13051 Cov.: 0

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

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.: 39 AF XY: 0.390 AC XY: 265653 AN XY: 681934

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

GnomAD4 genome AF: 0.392 AC: 58785 AN: 149850 Hom.: 13066 Cov.: 0 AF XY: 0.390 AC XY: 28486 AN XY: 73048

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

Alfa AF: 0.278 Hom.: 868

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.32
Mutation Taster		=73/27	polymorphism (auto)

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; COSMIC: COSV58272668; COSMIC: COSV58272668;