2-71071822-C-G

Variant names:

• chr2-71071822-C-G
• rs760520349
• NM_017567.6:c.350C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017567.6(NAGK):​c.350C>G​(p.Pro117Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. P117L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NAGK NM_017567.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 1 publications found

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]

ACMG classification

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=0.12311524).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAGK	NM_017567.6	MANE Select	c.350C>G	p.Pro117Arg	missense	Exon 4 of 10	NP_060037.4
	NAGK	NM_001330425.3		c.197C>G	p.Pro66Arg	missense	Exon 3 of 9	NP_001317354.1	C9JEV6
	NAGK	NM_001330426.2		c.197C>G	p.Pro66Arg	missense	Exon 4 of 10	NP_001317355.1	C9JEV6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAGK	ENST00000244204.11	TSL:1 MANE Select	c.350C>G	p.Pro117Arg	missense	Exon 4 of 10	ENSP00000244204.5	Q9UJ70-1
	NAGK	ENST00000455662.6	TSL:1	c.488C>G	p.Pro163Arg	missense	Exon 4 of 10	ENSP00000389087.2	Q9UJ70-2
	NAGK	ENST00000613852.4	TSL:1	c.488C>G	p.Pro163Arg	missense	Exon 4 of 10	ENSP00000477639.1	Q9UJ70-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 250970 AF XY: 0.00000737

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: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461686 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727150

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111938

Other (OTH) AF: 0.0000166 AC: 1 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	23
DANN	Benign	0.87
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.43	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N
PhyloP100		1.2
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.054
Sift	Benign	0.23	T
Sift4G	Benign	0.32	T
Polyphen		0.21	B
Vest4		0.49
MutPred		0.41		Loss of glycosylation at T114 (P = 0.0175)
MVP		0.48
MPC		0.092
ClinPred		0.096	T
GERP RS		2.4
PromoterAI		-0.31	Neutral
Varity_R		0.094
gMVP		0.71
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs760520349; hg19: chr2-71298952;