14-52778346-C-T

Variant names:

• chr14-52778346-C-T
• NM_198066.4:c.520G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_198066.4(GNPNAT1):​c.520G>A​(p.Glu174Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GNPNAT1 NM_198066.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.82

Genes affected

GNPNAT1 (HGNC:19980): (glucosamine-phosphate N-acetyltransferase 1) Enables identical protein binding activity. Predicted to be involved in UDP-N-acetylglucosamine biosynthetic process. Predicted to act upstream of or within cellular response to leukemia inhibitory factor. Predicted to be located in late endosome. Predicted to be active in Golgi apparatus; endoplasmic reticulum; and endoplasmic reticulum-Golgi intermediate compartment. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38595676).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNPNAT1	NM_198066.4	c.520G>A	p.Glu174Lys	missense_variant	Exon 6 of 6	ENST00000216410.8	NP_932332.1
GNPNAT1	XM_005268012.4	c.520G>A	p.Glu174Lys	missense_variant	Exon 7 of 7		XP_005268069.1
GNPNAT1	XM_006720238.4	c.520G>A	p.Glu174Lys	missense_variant	Exon 6 of 6		XP_006720301.1
GNPNAT1	XM_047431705.1	c.520G>A	p.Glu174Lys	missense_variant	Exon 7 of 7		XP_047287661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNPNAT1	ENST00000216410.8	c.520G>A	p.Glu174Lys	missense_variant	Exon 6 of 6	1	NM_198066.4	ENSP00000216410.3
GNPNAT1	ENST00000650397.1	c.520G>A	p.Glu174Lys	missense_variant	Exon 6 of 7			ENSP00000496934.1
GNPNAT1	ENST00000554230.5	c.307G>A	p.Glu103Lys	missense_variant	Exon 5 of 5	5		ENSP00000452310.1
GNPNAT1	ENST00000557604.1	c.*29G>A		downstream_gene_variant		3		ENSP00000452032.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 09, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.520G>A (p.E174K) alteration is located in exon 6 (coding exon 5) of the GNPNAT1 gene. This alteration results from a G to A substitution at nucleotide position 520, causing the glutamic acid (E) at amino acid position 174 to be replaced by a lysine (K). 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	0.12
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T;T;.
Eigen	Benign	0.037
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	.;D;D
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.39	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.6	L;L;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.59	N;.;N
REVEL	Benign	0.12
Sift	Benign	0.21	T;.;T
Sift4G	Benign	0.39	T;.;T
Polyphen		0.0090	B;B;.
Vest4		0.33
MutPred		0.58		Gain of MoRF binding (P = 3e-04);Gain of MoRF binding (P = 3e-04);.;
MVP		0.69
MPC		0.46
ClinPred		0.89	D
GERP RS		5.7
Varity_R		0.31
gMVP		0.84

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-53245064;