chr2-71068606-C-G

Variant names:

• chr2-71068606-C-G
• rs372401395
• ENST00000455662.6:c.61C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000455662.6(NAGK):​c.61C>G​(p.Pro21Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,524,010 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00065 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (1 hom.)
• Consequence: NAGK ENST00000455662.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.13
• Publications: 2 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]

ENSG00000272735 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007443726).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAGK	NM_001330426.2		c.-125+270C>G		intron	N/A	NP_001317355.1	C9JEV6
	NAGK	NM_017567.6	MANE Select	c.-78C>G		upstream_gene	N/A	NP_060037.4
	NAGK	NM_001330425.3		c.-146C>G		upstream_gene	N/A	NP_001317354.1	C9JEV6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAGK	ENST00000455662.6	TSL:1	c.61C>G	p.Pro21Ala	missense	Exon 1 of 10	ENSP00000389087.2	Q9UJ70-2
	NAGK	ENST00000613852.4	TSL:1	c.61C>G	p.Pro21Ala	missense	Exon 1 of 10	ENSP00000477639.1	Q9UJ70-2
	NAGK	ENST00000868350.1		c.-78C>G		5_prime_UTR	Exon 1 of 10	ENSP00000538409.1

Frequencies

GnomAD3 genomes AF: 0.000650 AC: 99 AN: 152238 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00103

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000483 AC: 62 AN: 128408 AF XY: 0.000494

Gnomad AFR exome AF: 0.000178

Gnomad AMR exome AF: 0.000355

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000668

Gnomad NFE exome AF: 0.00108

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00116 AC: 1591 AN: 1371654 Hom.: 1 Cov.: 30 AF XY: 0.00113 AC XY: 765 AN XY: 676552

African (AFR) AF: 0.000349 AC: 10 AN: 28668

American (AMR) AF: 0.000256 AC: 8 AN: 31296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24190

East Asian (EAS) AF: 0.00 AC: 0 AN: 31982

South Asian (SAS) AF: 0.0000645 AC: 5 AN: 77478

European-Finnish (FIN) AF: 0.000143 AC: 7 AN: 48850

Middle Eastern (MID) AF: 0.000210 AC: 1 AN: 4764

European-Non Finnish (NFE) AF: 0.00141 AC: 1505 AN: 1067712

Other (OTH) AF: 0.000970 AC: 55 AN: 56714

GnomAD4 genome AF: 0.000650 AC: 99 AN: 152356 Hom.: 0 Cov.: 33 AF XY: 0.000550 AC XY: 41 AN XY: 74504

African (AFR) AF: 0.000192 AC: 8 AN: 41586

American (AMR) AF: 0.000522 AC: 8 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00103 AC: 70 AN: 68026

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000684 Hom.: 0

Bravo AF: 0.000620

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000723 AC: 1

ESP6500EA AF: 0.00126 AC: 4

ExAC AF: 0.000209 AC: 6

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Benign	0.85
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.0074	T
MetaSVM	Benign	-1.0	T
PhyloP100		3.1
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.040
Sift	Pathogenic	0.0	D
Vest4		0.15
MVP		0.17
MPC		0.20
ClinPred		0.18	T
GERP RS		3.8
PromoterAI		-0.071	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.23
Mutation Taster		=90/10	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs372401395; hg19: chr2-71295736; COSMIC: COSV99730411; COSMIC: COSV99730411;