chr2-71071822-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017567.6(NAGK):​c.350C>T​(p.Pro117Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 32)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

NAGK
NM_017567.6 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.23
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14182523).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NAGKNM_017567.6 linkc.350C>T p.Pro117Leu missense_variant Exon 4 of 10 ENST00000244204.11 NP_060037.4 Q9UJ70-1A0A384N6G7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NAGKENST00000244204.11 linkc.350C>T p.Pro117Leu missense_variant Exon 4 of 10 1 NM_017567.6 ENSP00000244204.5 Q9UJ70-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152170
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
250970
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135728
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.0000579
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000465
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000178
AC:
26
AN:
1461686
Hom.:
0
Cov.:
30
AF XY:
0.0000138
AC XY:
10
AN XY:
727150
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000202
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000188
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152170
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000247
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 01, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.488C>T (p.P163L) alteration is located in exon 4 (coding exon 4) of the NAGK gene. This alteration results from a C to T substitution at nucleotide position 488, causing the proline (P) at amino acid position 163 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.096
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.46
CADD
Uncertain
23
DANN
Benign
0.94
DEOGEN2
Benign
0.28
.;.;T;T;T;.;.
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.26
FATHMM_MKL
Benign
0.40
N
LIST_S2
Uncertain
0.94
D;.;D;D;D;D;D
M_CAP
Benign
0.0084
T
MetaRNN
Benign
0.14
T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.81
.;.;.;.;L;.;.
PrimateAI
Benign
0.43
T
PROVEAN
Uncertain
-3.0
.;D;D;.;D;.;D
REVEL
Benign
0.046
Sift
Benign
0.11
.;T;T;.;T;.;T
Sift4G
Benign
0.17
T;T;T;T;T;T;T
Polyphen
0.54
.;.;.;.;P;.;.
Vest4
0.47
MutPred
0.40
.;.;.;Loss of loop (P = 0.0128);Loss of loop (P = 0.0128);.;.;
MVP
0.58
MPC
0.088
ClinPred
0.28
T
GERP RS
2.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.15
gMVP
0.69

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs760520349; hg19: chr2-71298952; API