Genetic Variant ENST00000455662.6:c.79A>G (chr2-71068624-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000455662.6(NAGK):c.79A>G(p.Arg27Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000292 in 1,368,852 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 Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

NAGK
ENST00000455662.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.706

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: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05158317).

BP6

Variant 2-71068624-A-G is Benign according to our data. Variant chr2-71068624-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3402541.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000455662.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NAGK	NM_001330426.2		c.-125+288A>G	intron	N/A	NP_001317355.1	C9JEV6
NAGK	NM_017567.6	MANE Select	c.-60A>G	upstream_gene	N/A	NP_060037.4
NAGK	NM_001330425.3		c.-128A>G	upstream_gene	N/A	NP_001317354.1	C9JEV6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NAGK	ENST00000455662.6	TSL:1	c.79A>G	p.Arg27Gly	missense	Exon 1 of 10	ENSP00000389087.2	Q9UJ70-2
NAGK	ENST00000613852.4	TSL:1	c.79A>G	p.Arg27Gly	missense	Exon 1 of 10	ENSP00000477639.1	Q9UJ70-2
NAGK	ENST00000951785.1		c.-60A>G		5_prime_UTR	Exon 1 of 10	ENSP00000621844.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000292

AC:

AN:

1368852

Hom.:

Cov.:

AF XY:

0.00000444

AC XY:

AN XY:

675506

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28450

American (AMR)

AF:

0.00

AC:

AN:

30112

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24072

East Asian (EAS)

AF:

0.00

AC:

AN:

31606

South Asian (SAS)

AF:

0.00

AC:

AN:

77172

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48892

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4982

European-Non Finnish (NFE)

AF:

0.00000281

AC:

AN:

1066956

Other (OTH)

AF:

0.0000177

AC:

AN:

56610

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Likely benign

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

Benign

0.066

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

2.4

(source)

DANN

Benign

0.47

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0013

LIST_S2

Benign

0.22

M_CAP

Benign

0.0072

MetaRNN

Benign

0.052

MetaSVM

Benign

-1.0

PhyloP100

-0.71

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.23

REVEL

Benign

0.0060

Sift

Benign

0.43

Sift4G

Pathogenic

0.0

Vest4

0.037

MutPred

0.24

Loss of MoRF binding (P = 0.0497)

MVP

0.076

MPC

0.077

ClinPred

0.12

GERP RS

1.1

PromoterAI

-0.055

Neutral

(source)

gMVP

0.43

Mutation Taster

=93/7

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over