chr3-25729275-G-T

Variant names:

• chr3-25729275-G-T
• NM_018297.4:c.1469C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018297.4(NGLY1):​c.1469C>A​(p.Ser490Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000748 in 1,337,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: NGLY1 NM_018297.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

Genes affected

NGLY1 (HGNC:17646): (N-glycanase 1) This gene encodes an enzyme that catalyzes hydrolysis of an N(4)-(acetyl-beta-D-glucosaminyl) asparagine residue to N-acetyl-beta-D-glucosaminylamine and a peptide containing an aspartate residue. The encoded enzyme may play a role in the proteasome-mediated degradation of misfolded glycoproteins. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2009]

ACMG classification

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=0.24811241).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NGLY1	NM_018297.4	c.1469C>A	p.Ser490Tyr	missense_variant	Exon 10 of 12	ENST00000280700.10	NP_060767.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NGLY1	ENST00000280700.10	c.1469C>A	p.Ser490Tyr	missense_variant	Exon 10 of 12	1	NM_018297.4	ENSP00000280700.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.48e-7 AC: 1 AN: 1337446 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 660430

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.59e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	.;T;.;T;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.86	D;D;D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.25	T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.6	.;M;M;.;.
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.5	D;D;D;D;D
REVEL	Benign	0.078
Sift	Benign	0.036	D;T;D;D;T
Sift4G	Uncertain	0.037	D;D;D;T;D
Polyphen		0.91	P;P;P;.;.
Vest4		0.35
MutPred		0.37		.;Loss of disorder (P = 0.0612);Loss of disorder (P = 0.0612);.;.;
MVP		0.56
MPC		0.12
ClinPred		0.93	D
GERP RS		4.0
Varity_R		0.095
gMVP		0.57

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: chr3-25770766;