rs760520349

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr2-71071822-C-A
• chr2-71071822-C-G
• chr2-71071822-C-T

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>A​(p.Pro117Gln) 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 152,170 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: 𝑓 0.0000066 (0 hom., cov: 32)
• 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=0.07435346).

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>A	p.Pro117Gln	missense	Exon 4 of 10	NP_060037.4
	NAGK	NM_001330425.3		c.197C>A	p.Pro66Gln	missense	Exon 3 of 9	NP_001317354.1	C9JEV6
	NAGK	NM_001330426.2		c.197C>A	p.Pro66Gln	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>A	p.Pro117Gln	missense	Exon 4 of 10	ENSP00000244204.5	Q9UJ70-1
	NAGK	ENST00000455662.6	TSL:1	c.488C>A	p.Pro163Gln	missense	Exon 4 of 10	ENSP00000389087.2	Q9UJ70-2
	NAGK	ENST00000613852.4	TSL:1	c.488C>A	p.Pro163Gln	missense	Exon 4 of 10	ENSP00000477639.1	Q9UJ70-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152170 Hom.: 0 Cov.: 32

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

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152170 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74348

African (AFR) AF: 0.0000241 AC: 1 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Benign	0.91
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.26	N
PhyloP100		1.2
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.20	N
REVEL	Benign	0.032
Sift	Benign	0.31	T
Sift4G	Benign	0.41	T
Polyphen		0.0010	B
Vest4		0.24
MutPred		0.38		Loss of sheet (P = 0.0181)
MVP		0.37
MPC		0.061
ClinPred		0.11	T
GERP RS		2.4
PromoterAI		-0.25	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.089
gMVP		0.66
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs760520349; hg19: chr2-71298952; COSMIC: COSV54903716; COSMIC: COSV54903716;