1-1752908-C-CCCT

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NADK	NM_023018.5	c.1334_1336dupAGG	p.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.1334_1336dupAGG	p.Glu445dup	conservative_inframe_insertion	Exon 12 of 12	2	NM_023018.5	ENSP00000341679.5

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

GnomAD3 exomes AF: 0.374 AC: 60843 AN: 162868 Hom.: 4553 AF XY: 0.370 AC XY: 32322 AN XY: 87258

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 SAS exome AF: 0.314

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

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.437

Gnomad4 ASJ exome AF: 0.327

Gnomad4 EAS exome AF: 0.319

Gnomad4 SAS exome AF: 0.270

Gnomad4 FIN exome AF: 0.410

Gnomad4 NFE exome AF: 0.417

Gnomad4 OTH exome AF: 0.377

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

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.383

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.410

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 12, 2023

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs71578334; hg19: chr1-1684347;