chr1-1752908-CCCT-C

Variant names:

• chr1-1752908-CCCT-C
• rs71578334
• NM_023018.5:c.1334_1336delAGG

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP3 BA1

The NM_023018.5(NADK):​c.1334_1336delAGG​(p.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 0.00645 in 1,467,238 control chromosomes in the GnomAD database, including 135 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.020 (76 hom., cov: 0)
  • Exomes 𝑓: 0.0049 (59 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: Benign. The variant received -9 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_023018.5
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NADK	NM_023018.5	c.1334_1336delAGG	p.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.1334_1336delAGG	p.Glu445del	disruptive_inframe_deletion	Exon 12 of 12	2	NM_023018.5	ENSP00000341679.5

Frequencies

GnomAD3 genomes AF: 0.0201 AC: 3013 AN: 149788 Hom.: 67 Cov.: 0

Gnomad AFR AF: 0.0594

Gnomad AMI AF: 0.00111

Gnomad AMR AF: 0.0189

Gnomad ASJ AF: 0.00116

Gnomad EAS AF: 0.00139

Gnomad SAS AF: 0.000851

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.00156

Gnomad OTH AF: 0.0171

GnomAD2 exomes AF: 0.0148 AC: 2411 AN: 162868 AF XY: 0.0136

Gnomad AFR exome AF: 0.0708

Gnomad AMR exome AF: 0.0140

Gnomad ASJ exome AF: 0.0116

Gnomad EAS exome AF: 0.00646

Gnomad FIN exome AF: 0.0163

Gnomad NFE exome AF: 0.00837

Gnomad OTH exome AF: 0.0137

GnomAD4 exome AF: 0.00486 AC: 6407 AN: 1317340 Hom.: 59 AF XY: 0.00473 AC XY: 3077 AN XY: 650634

African (AFR) AF: 0.0719 AC: 2141 AN: 29798

American (AMR) AF: 0.0123 AC: 432 AN: 35248

Ashkenazi Jewish (ASJ) AF: 0.00560 AC: 129 AN: 23024

East Asian (EAS) AF: 0.00309 AC: 106 AN: 34352

South Asian (SAS) AF: 0.00624 AC: 451 AN: 72230

European-Finnish (FIN) AF: 0.0115 AC: 537 AN: 46496

Middle Eastern (MID) AF: 0.00864 AC: 46 AN: 5322

European-Non Finnish (NFE) AF: 0.00210 AC: 2136 AN: 1016616

Other (OTH) AF: 0.00791 AC: 429 AN: 54254

GnomAD4 genome AF: 0.0204 AC: 3061 AN: 149898 Hom.: 76 Cov.: 0 AF XY: 0.0203 AC XY: 1487 AN XY: 73072

African (AFR) AF: 0.0604 AC: 2480 AN: 41028

American (AMR) AF: 0.0189 AC: 284 AN: 15022

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

East Asian (EAS) AF: 0.00139 AC: 7 AN: 5030

South Asian (SAS) AF: 0.000853 AC: 4 AN: 4692

European-Finnish (FIN) AF: 0.0136 AC: 139 AN: 10204

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.00156 AC: 105 AN: 67212

Other (OTH) AF: 0.0170 AC: 35 AN: 2062

Alfa AF: 0.0232 Hom.: 868

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.43
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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: COSV58269800; COSMIC: COSV58269800;