chr1-1757129-C-T

Variant names:

• chr1-1757129-C-T
• rs754012182
• ENST00000378625.5:c.757G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001198994.2(NADK):​c.757G>A​(p.Ala253Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000179 in 1,540,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: NADK NM_001198994.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.56
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.056464046).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198994.2. 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.393+52G>A		intron	N/A	NP_075394.3
	NADK	NM_001198994.2		c.757G>A	p.Ala253Thr	missense	Exon 6 of 14	NP_001185923.1	O95544-2
	NADK	NM_001198993.2		c.393+52G>A		intron	N/A	NP_001185922.1	O95544-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NADK	ENST00000378625.5	TSL:1	c.757G>A	p.Ala253Thr	missense	Exon 6 of 14	ENSP00000367890.1	O95544-2
	NADK	ENST00000341426.9	TSL:2 MANE Select	c.393+52G>A		intron	N/A	ENSP00000341679.5	O95544-1
	NADK	ENST00000341991.7	TSL:1	c.393+52G>A		intron	N/A	ENSP00000344340.3	O95544-1

Frequencies

GnomAD3 genomes AF: 0.0000922 AC: 14 AN: 151906 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000711 AC: 11 AN: 154624 AF XY: 0.0000599

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000397

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000169

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000188 AC: 261 AN: 1388684 Hom.: 0 Cov.: 31 AF XY: 0.000175 AC XY: 120 AN XY: 684982

African (AFR) AF: 0.0000317 AC: 1 AN: 31562

American (AMR) AF: 0.000111 AC: 4 AN: 36092

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24976

East Asian (EAS) AF: 0.00 AC: 0 AN: 35910

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79068

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4044

European-Non Finnish (NFE) AF: 0.000228 AC: 244 AN: 1071922

Other (OTH) AF: 0.000191 AC: 11 AN: 57520

GnomAD4 genome AF: 0.0000922 AC: 14 AN: 151906 Hom.: 0 Cov.: 31 AF XY: 0.0000809 AC XY: 6 AN XY: 74162

African (AFR) AF: 0.0000484 AC: 2 AN: 41338

American (AMR) AF: 0.000131 AC: 2 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5134

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 67976

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.0000671 Hom.: 0

Bravo AF: 0.000162

ExAC AF: 0.000159 AC: 16

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	0.079
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.46
DANN	Benign	0.68
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0020	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.1	T
PhyloP100		-1.6
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.019
Sift	Benign	0.22	T
Sift4G	Benign	0.74	T
Vest4		0.23
MVP		0.048
ClinPred		0.017	T
GERP RS		-1.5
PromoterAI		-0.0059	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
gMVP		0.16
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs754012182; hg19: chr1-1688568;