1-1752908-CCCTCCTCCTCCTCCTCCT-CCCTCCTCCTCCTCCTCCTCCTCCT

Variant names:

• chr1-1752908-C-CCCTCCT
• rs71578334
• NM_023018.5:c.1331_1336dupAGGAGG

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP3 BS1 BS2

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
• 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: 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

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.1331_1336dupAGGAGG	p.Glu444_Glu445dup	conservative_inframe_insertion	Exon 12 of 12	NP_075394.3
	NADK	NM_001198994.2		c.1766_1771dupAGGAGG	p.Glu589_Glu590dup	conservative_inframe_insertion	Exon 14 of 14	NP_001185923.1	O95544-2
	NADK	NM_001198993.2		c.1331_1336dupAGGAGG	p.Glu444_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.1331_1336dupAGGAGG	p.Glu444_Glu445dup	conservative_inframe_insertion	Exon 12 of 12	ENSP00000341679.5	O95544-1
	NADK	ENST00000378625.5	TSL:1	c.1766_1771dupAGGAGG	p.Glu589_Glu590dup	conservative_inframe_insertion	Exon 14 of 14	ENSP00000367890.1	O95544-2
	NADK	ENST00000341991.7	TSL:1	c.1331_1336dupAGGAGG	p.Glu444_Glu445dup	conservative_inframe_insertion	Exon 12 of 12	ENSP00000344340.3	O95544-1

Frequencies

GnomAD3 genomes AF: 0.00443 AC: 663 AN: 149830 Hom.: 2 Cov.: 0

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

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.: 11 Cov.: 39 AF XY: 0.00442 AC XY: 3019 AN XY: 682320

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: 38 AN: 24796

East Asian (EAS) AF: 0.00256 AC: 95 AN: 37176

South Asian (SAS) AF: 0.0211 AC: 1716 AN: 81210

European-Finnish (FIN) AF: 0.000349 AC: 17 AN: 48668

Middle Eastern (MID) AF: 0.0130 AC: 73 AN: 5610

European-Non Finnish (NFE) AF: 0.00277 AC: 2913 AN: 1051898

Other (OTH) AF: 0.00480 AC: 274 AN: 57088

GnomAD4 genome AF: 0.00440 AC: 660 AN: 149940 Hom.: 2 Cov.: 0 AF XY: 0.00471 AC XY: 344 AN XY: 73090

African (AFR) AF: 0.00422 AC: 173 AN: 41038

American (AMR) AF: 0.00373 AC: 56 AN: 15022

Ashkenazi Jewish (ASJ) AF: 0.00116 AC: 4 AN: 3454

East Asian (EAS) AF: 0.00417 AC: 21 AN: 5030

South Asian (SAS) AF: 0.0232 AC: 109 AN: 4692

European-Finnish (FIN) AF: 0.000587 AC: 6 AN: 10216

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.00378 AC: 254 AN: 67230

Other (OTH) AF: 0.0107 AC: 22 AN: 2064

Alfa AF: 0.00435 Hom.: 868

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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;