chr1-1752977-T-C

Variant names:

• chr1-1752977-T-C
• NM_023018.5:c.1268A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_023018.5(NADK):​c.1268A>G​(p.Gln423Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,450,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NADK NM_023018.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.56
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17491695).

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.1268A>G	p.Gln423Arg	missense	Exon 12 of 12	NP_075394.3
	NADK	NM_001198994.2		c.1703A>G	p.Gln568Arg	missense	Exon 14 of 14	NP_001185923.1	O95544-2
	NADK	NM_001198993.2		c.1268A>G	p.Gln423Arg	missense	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.1268A>G	p.Gln423Arg	missense	Exon 12 of 12	ENSP00000341679.5	O95544-1
	NADK	ENST00000378625.5	TSL:1	c.1703A>G	p.Gln568Arg	missense	Exon 14 of 14	ENSP00000367890.1	O95544-2
	NADK	ENST00000341991.7	TSL:1	c.1268A>G	p.Gln423Arg	missense	Exon 12 of 12	ENSP00000344340.3	O95544-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1450168 Hom.: 0 Cov.: 56 AF XY: 0.00 AC XY: 0 AN XY: 720310

African (AFR) AF: 0.00 AC: 0 AN: 33406

American (AMR) AF: 0.00 AC: 0 AN: 41710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25818

East Asian (EAS) AF: 0.00 AC: 0 AN: 39330

South Asian (SAS) AF: 0.00 AC: 0 AN: 84644

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52470

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1106976

Other (OTH) AF: 0.00 AC: 0 AN: 60052

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Benign	0.75
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.0073
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		5.6
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.11
Sift	Benign	0.43	T
Sift4G	Benign	0.63	T
Polyphen		0.29	B
Vest4		0.22
MutPred		0.39		Gain of MoRF binding (P = 0.0134)
MVP		0.51
ClinPred		0.49	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.38
Mutation Taster		=66/34	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

hg19: chr1-1684416;