1-1760748-C-A

Variant names:

• chr1-1760748-C-A
• rs7366653
• NM_023018.5:c.263+1204G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_023018.5(NADK):​c.263+1204G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 150,548 control chromosomes in the GnomAD database, including 108 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.013 (108 hom., cov: 33)
• Consequence: NADK NM_023018.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NADK	NM_023018.5	c.263+1204G>T		intron_variant	Intron 3 of 11	ENST00000341426.9	NP_075394.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NADK	ENST00000341426.9	c.263+1204G>T		intron_variant	Intron 3 of 11	2	NM_023018.5	ENSP00000341679.5

Frequencies

GnomAD3 genomes AF: 0.0133 AC: 2005 AN: 150428 Hom.: 109 Cov.: 33

Gnomad AFR AF: 0.00216

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0990

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000831

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00518

Gnomad OTH AF: 0.0145

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0134 AC: 2010 AN: 150548 Hom.: 108 Cov.: 33 AF XY: 0.0149 AC XY: 1095 AN XY: 73640

African (AFR) AF: 0.00215 AC: 87 AN: 40452

American (AMR) AF: 0.0992 AC: 1507 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 15 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5096

South Asian (SAS) AF: 0.000832 AC: 4 AN: 4806

European-Finnish (FIN) AF: 0.00151 AC: 16 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00519 AC: 351 AN: 67694

Other (OTH) AF: 0.0143 AC: 30 AN: 2094

Alfa AF: 0.00301 Hom.: 1

Bravo AF: 0.0199

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.47
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

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: rs7366653; hg19: chr1-1692187;