1-1752908-CCCTCCTCCTCCTCCTCCT-CCCTCCTCCTCCTCCTCCTCCTCCTCCTCCTCCTCCT

Variant names:

• chr1-1752908-C-CCCTCCTCCTCCTCCTCCT
• rs71578334
• NM_023018.5:c.1319_1336dupAGGAGGAGGAGGAGGAGG

Variant summary

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

The NM_023018.5(NADK):​c.1319_1336dupAGGAGGAGGAGGAGGAGG​(p.Glu440_Glu445dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000051 (0 hom.)
  • Failed GnomAD Quality Control
• 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.1319_1336dupAGGAGGAGGAGGAGGAGG	p.Glu440_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.1319_1336dupAGGAGGAGGAGGAGGAGG	p.Glu440_Glu445dup	conservative_inframe_insertion	Exon 12 of 12	2	NM_023018.5	ENSP00000341679.5

Frequencies

GnomAD3 genomes AF: 0.0000200 AC: 3 AN: 149844 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000200

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000509 AC: 7 AN: 1376176 Hom.: 0 Cov.: 39 AF XY: 0.00000440 AC XY: 3 AN XY: 682498

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32716

American (AMR) AF: 0.000136 AC: 5 AN: 36648

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 37178

South Asian (SAS) AF: 0.00 AC: 0 AN: 81228

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: 0.00 AC: 0 AN: 1052230

Other (OTH) AF: 0.0000350 AC: 2 AN: 57098

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000200 AC: 3 AN: 149844 Hom.: 0 Cov.: 0 AF XY: 0.0000274 AC XY: 2 AN XY: 72972

African (AFR) AF: 0.00 AC: 0 AN: 40922

American (AMR) AF: 0.000200 AC: 3 AN: 15004

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5044

South Asian (SAS) AF: 0.00 AC: 0 AN: 4698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10218

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67242

Other (OTH) AF: 0.00 AC: 0 AN: 2046

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;