Variant 16-5033482-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016256.4(NAGPA):c.333A>G(p.Gly111Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 1,569,762 control chromosomes in the GnomAD database, including 365,006 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 35068 hom., cov: 33)

Exomes 𝑓: 0.68 ( 329938 hom. )

Consequence

NAGPA
NM_016256.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.42

Variant links:

Genes affected

NAGPA (HGNC:17378): (N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase) Hydrolases are transported to lysosomes after binding to mannose 6-phosphate receptors in the trans-Golgi network. This gene encodes the enzyme that catalyzes the second step in the formation of the mannose 6-phosphate recognition marker on lysosomal hydrolases. Commonly known as 'uncovering enzyme' or UCE, this enzyme removes N-acetyl-D-glucosamine (GlcNAc) residues from GlcNAc-alpha-P-mannose moieties and thereby produces the recognition marker. The encoded preproprotein is proteolytically processed by furin to generate the mature enzyme, a homotetramer of two disulfide-linked homodimers. Mutations in this gene are associated with developmental stuttering in human patients. [provided by RefSeq, Oct 2015]

NAGPA links:

NAGPA (HGNC:):

NAGPA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 16-5033482-T-C is Benign according to our data. Variant chr16-5033482-T-C is described in ClinVar as [Benign]. Clinvar id is 260706.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.42 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAGPA	NM_016256.4 linkuse as main transcript	c.333A>G	p.Gly111Gly	synonymous_variant	2/10	ENST00000312251.8	NP_057340.2	Q9UK23-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAGPA	ENST00000312251.8 linkuse as main transcript	c.333A>G	p.Gly111Gly	synonymous_variant	2/10	1	NM_016256.4	ENSP00000310998.3		Q9UK23-1

Frequencies

GnomAD3 genomes

AF:

0.676

AC:

102641

AN:

151838

Hom.:

35029

Cov.:

show subpopulations

Gnomad AFR

AF:

0.660

Gnomad AMI

AF:

0.675

Gnomad AMR

AF:

0.713

Gnomad ASJ

AF:

0.692

Gnomad EAS

AF:

0.837

Gnomad SAS

AF:

0.825

Gnomad FIN

AF:

0.536

Gnomad MID

AF:

0.838

Gnomad NFE

AF:

0.674

Gnomad OTH

AF:

0.698

GnomAD3 exomes

AF:

0.705

AC:

126817

AN:

179764

Hom.:

45310

AF XY:

0.711

AC XY:

71363

AN XY:

100394

show subpopulations

Gnomad AFR exome

AF:

0.646

Gnomad AMR exome

AF:

0.733

Gnomad ASJ exome

AF:

0.701

Gnomad EAS exome

AF:

0.836

Gnomad SAS exome

AF:

0.822

Gnomad FIN exome

AF:

0.542

Gnomad NFE exome

AF:

0.656

Gnomad OTH exome

AF:

0.696

GnomAD4 exome

AF:

0.680

AC:

963771

AN:

1417812

Hom.:

329938

Cov.:

AF XY:

0.685

AC XY:

481441

AN XY:

703192

show subpopulations

Gnomad4 AFR exome

AF:

0.662

Gnomad4 AMR exome

AF:

0.727

Gnomad4 ASJ exome

AF:

0.696

Gnomad4 EAS exome

AF:

0.820

Gnomad4 SAS exome

AF:

0.825

Gnomad4 FIN exome

AF:

0.550

Gnomad4 NFE exome

AF:

0.665

Gnomad4 OTH exome

AF:

0.698

GnomAD4 genome

AF:

0.676

AC:

102729

AN:

151950

Hom.:

35068

Cov.:

AF XY:

0.676

AC XY:

50190

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.660

Gnomad4 AMR

AF:

0.713

Gnomad4 ASJ

AF:

0.692

Gnomad4 EAS

AF:

0.837

Gnomad4 SAS

AF:

0.825

Gnomad4 FIN

AF:

0.536

Gnomad4 NFE

AF:

0.674

Gnomad4 OTH

AF:

0.701

Alfa

AF:

0.670

Hom.:

6120

Bravo

AF:

0.686

Asia WGS

AF:

0.811

AC:

2805

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

9.4

DANN

Benign

0.53

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over