Variant chr16-5027351-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_016256.4(NAGPA):c.1203C>G(p.Gly401Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,614,112 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0010 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 13 hom. )

Consequence

NAGPA
NM_016256.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.01

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 16-5027351-G-C is Benign according to our data. Variant chr16-5027351-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 707823.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.01 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAGPA	NM_016256.4 linkuse as main transcript	c.1203C>G	p.Gly401Gly	synonymous_variant	8/10	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.1203C>G	p.Gly401Gly	synonymous_variant	8/10	1	NM_016256.4	ENSP00000310998.3		Q9UK23-1

Frequencies

GnomAD3 genomes

AF:

0.00101

AC:

153

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.000848

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00146

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00129

AC:

324

AN:

251170

Hom.:

AF XY:

0.00153

AC XY:

208

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.000893

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00431

Gnomad FIN exome

AF:

0.000648

Gnomad NFE exome

AF:

0.00117

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00115

AC:

1677

AN:

1461850

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

937

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000581

Gnomad4 ASJ exome

AF:

0.000842

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00467

Gnomad4 FIN exome

AF:

0.000599

Gnomad4 NFE exome

AF:

0.000963

Gnomad4 OTH exome

AF:

0.00116

GnomAD4 genome

AF:

0.00101

AC:

154

AN:

152262

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.000848

Gnomad4 NFE

AF:

0.00146

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00140

Hom.:

Bravo

AF:

0.000748

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.00207

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 06, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	NAGPA: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

6.5

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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