Genetic Variant NADK:p.Ala253Ser (chr1-1757129-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001198994.2(NADK):c.757G>T(p.Ala253Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A253T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NADK
NM_001198994.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.56

Publications

1 publications found

Variant links:

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]

NADK links:

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ACMG classification

Classification was made for transcript

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=0.088962555).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NADK	NM_023018.5	MANE Select	c.393+52G>T		intron	N/A	NP_075394.3
NADK	NM_001198994.2		c.757G>T	p.Ala253Ser	missense	Exon 6 of 14	NP_001185923.1	O95544-2
NADK	NM_001198993.2		c.393+52G>T		intron	N/A	NP_001185922.1	O95544-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NADK	ENST00000378625.5	TSL:1	c.757G>T	p.Ala253Ser	missense	Exon 6 of 14	ENSP00000367890.1	O95544-2
NADK	ENST00000341426.9	TSL:2 MANE Select	c.393+52G>T		intron	N/A	ENSP00000341679.5	O95544-1
NADK	ENST00000341991.7	TSL:1	c.393+52G>T		intron	N/A	ENSP00000344340.3	O95544-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

154624

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1388694

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

684990

African (AFR)

AF:

0.00

AC:

AN:

31562

American (AMR)

AF:

0.00

AC:

AN:

36092

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24976

East Asian (EAS)

AF:

0.00

AC:

AN:

35910

South Asian (SAS)

AF:

0.00

AC:

AN:

79068

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4044

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1071932

Other (OTH)

AF:

0.00

AC:

AN:

57520

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.30

(source)

DANN

Benign

0.52

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0087

LIST_S2

Benign

0.23

M_CAP

Benign

0.0030

MetaRNN

Benign

0.089

MetaSVM

Benign

-1.1

PhyloP100

-1.6

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.10

REVEL

Benign

0.028

Sift

Benign

0.23

Sift4G

Benign

0.87

Vest4

0.23

MutPred

0.44

Gain of glycosylation at A253 (P = 0.0151)

MVP

0.15

ClinPred

0.035

GERP RS

-1.5

PromoterAI

-0.0039

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

gMVP

0.20

Mutation Taster

=98/2

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over