Genetic Variant NM_017567.6:c.5C>T (chr2-71068688-C-T) – 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_017567.6(NAGK):c.5C>T(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,230 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: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NAGK
NM_017567.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.549

Publications

0 publications found

Variant links:

Genes affected

NAGK (HGNC:17174): (N-acetylglucosamine kinase) This gene encodes a member of the N-acetylhexosamine kinase family. The encoded protein catalyzes the conversion of N-acetyl-D-glucosamine to N-acetyl-D-glucosamine 6-phosphate, and is the major mammalian enzyme which recovers amino sugars. [provided by RefSeq, Nov 2011]

NAGK links:

ENSG00000272735 (HGNC:):

ENSG00000272735 links:

Genome browser will be placed here

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=0.115480274).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017567.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NAGK	NM_017567.6	MANE Select	c.5C>T	p.Ala2Val	missense	Exon 1 of 10	NP_060037.4
NAGK	NM_001330425.3		c.-64C>T		5_prime_UTR	Exon 1 of 9	NP_001317354.1	C9JEV6
NAGK	NM_001365466.2		c.-278C>T		5_prime_UTR	Exon 1 of 10	NP_001352395.1	C9JEV6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NAGK	ENST00000244204.11	TSL:1 MANE Select	c.5C>T	p.Ala2Val	missense	Exon 1 of 10	ENSP00000244204.5	Q9UJ70-1
NAGK	ENST00000455662.6	TSL:1	c.143C>T	p.Ala48Val	missense	Exon 1 of 10	ENSP00000389087.2	Q9UJ70-2
NAGK	ENST00000613852.4	TSL:1	c.143C>T	p.Ala48Val	missense	Exon 1 of 10	ENSP00000477639.1	Q9UJ70-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1366680

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

674118

African (AFR)

AF:

0.00

AC:

AN:

28432

American (AMR)

AF:

0.00

AC:

AN:

30848

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24134

East Asian (EAS)

AF:

0.00

AC:

AN:

30956

South Asian (SAS)

AF:

0.00

AC:

AN:

76702

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48900

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4712

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1065514

Other (OTH)

AF:

0.00

AC:

AN:

56482

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41466

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.25

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.51

M_CAP

Benign

0.032

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PhyloP100

0.55

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.31

REVEL

Benign

0.021

Sift

Benign

0.097

Sift4G

Benign

0.11

Polyphen

0.0

Vest4

0.087

MutPred

0.38

Gain of sheet (P = 0.0266)

MVP

0.20

MPC

0.062

ClinPred

0.49

GERP RS

2.4

PromoterAI

-0.18

Neutral

(source)

Varity_R

0.097

gMVP

0.24

Mutation Taster

=76/24

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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