Genetic Variant ENST00000455662.6:c.112G>C (chr2-71068657-G-C) – 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 ENST00000455662.6(NAGK):c.112G>C(p.Gly38Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000073 in 1,369,030 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. 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. G38W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

NAGK
ENST00000455662.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.139

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:

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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=0.08093706).

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_017567.6	MANE Select	c.-27G>C	5_prime_UTR	Exon 1 of 10	NP_060037.4
NAGK	NM_001330425.3		c.-95G>C	5_prime_UTR	Exon 1 of 9	NP_001317354.1	C9JEV6
NAGK	NM_001365466.2		c.-309G>C	5_prime_UTR	Exon 1 of 10	NP_001352395.1	C9JEV6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NAGK	ENST00000455662.6	TSL:1	c.112G>C	p.Gly38Arg	missense	Exon 1 of 10	ENSP00000389087.2	Q9UJ70-2
NAGK	ENST00000613852.4	TSL:1	c.112G>C	p.Gly38Arg	missense	Exon 1 of 10	ENSP00000477639.1	Q9UJ70-2
NAGK	ENST00000244204.11	TSL:1 MANE Select	c.-27G>C		5_prime_UTR	Exon 1 of 10	ENSP00000244204.5	Q9UJ70-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.30e-7

AC:

AN:

1369030

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

675368

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28620

American (AMR)

AF:

0.00

AC:

AN:

31346

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24208

East Asian (EAS)

AF:

0.00

AC:

AN:

31074

South Asian (SAS)

AF:

0.00

AC:

AN:

76936

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48930

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4990

European-Non Finnish (NFE)

AF:

9.38e-7

AC:

AN:

1066286

Other (OTH)

AF:

0.00

AC:

AN:

56640

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.9

(source)

DANN

Benign

0.75

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.45

M_CAP

Benign

0.015

MetaRNN

Benign

0.081

MetaSVM

Benign

-1.0

PhyloP100

0.14

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.20

REVEL

Benign

0.0060

Sift

Benign

0.076

Sift4G

Benign

0.067

Vest4

0.11

MutPred

0.23

Gain of MoRF binding (P = 0.0101)

MVP

0.19

MPC

0.10

ClinPred

0.21

GERP RS

0.20

PromoterAI

0.076

Neutral

(source)

gMVP

0.24

Mutation Taster

=94/6

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