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GeneBe

rs887854

chr16-5025541-G-Achr16-5025541-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_016256.4(NAGPA):c.1485C>T(p.Asn495=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 1,613,186 control chromosomes in the GnomAD database, including 365,164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.72 ( 40019 hom., cov: 35)
Exomes 𝑓: 0.66 ( 325145 hom. )

Consequence

NAGPA
NM_016256.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.656
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 16-5025541-G-A is Benign according to our data. Variant chr16-5025541-G-A is described in ClinVar as [Benign]. Clinvar id is 260705.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.656 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NAGPANM_016256.4 linkuse as main transcriptc.1485C>T p.Asn495= synonymous_variant 10/10 ENST00000312251.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NAGPAENST00000312251.8 linkuse as main transcriptc.1485C>T p.Asn495= synonymous_variant 10/101 NM_016256.4 P1Q9UK23-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.717
AC:
109047
AN:
152110
Hom.:
39962
Cov.:
35
show subpopulations
Gnomad AFR
AF:
0.860
Gnomad AMI
AF:
0.662
Gnomad AMR
AF:
0.710
Gnomad ASJ
AF:
0.654
Gnomad EAS
AF:
0.835
Gnomad SAS
AF:
0.817
Gnomad FIN
AF:
0.532
Gnomad MID
AF:
0.839
Gnomad NFE
AF:
0.647
Gnomad OTH
AF:
0.717
GnomAD3 exomes
AF:
0.697
AC:
175049
AN:
251280
Hom.:
62282
AF XY:
0.698
AC XY:
94854
AN XY:
135888
show subpopulations
Gnomad AFR exome
AF:
0.862
Gnomad AMR exome
AF:
0.721
Gnomad ASJ exome
AF:
0.663
Gnomad EAS exome
AF:
0.840
Gnomad SAS exome
AF:
0.818
Gnomad FIN exome
AF:
0.546
Gnomad NFE exome
AF:
0.643
Gnomad OTH exome
AF:
0.679
GnomAD4 exome
AF:
0.663
AC:
969259
AN:
1460958
Hom.:
325145
Cov.:
80
AF XY:
0.668
AC XY:
485382
AN XY:
726774
show subpopulations
Gnomad4 AFR exome
AF:
0.872
Gnomad4 AMR exome
AF:
0.716
Gnomad4 ASJ exome
AF:
0.655
Gnomad4 EAS exome
AF:
0.819
Gnomad4 SAS exome
AF:
0.817
Gnomad4 FIN exome
AF:
0.546
Gnomad4 NFE exome
AF:
0.641
Gnomad4 OTH exome
AF:
0.689
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.717
AC:
109166
AN:
152228
Hom.:
40019
Cov.:
35
AF XY:
0.716
AC XY:
53288
AN XY:
74426
show subpopulations
Gnomad4 AFR
AF:
0.860
Gnomad4 AMR
AF:
0.710
Gnomad4 ASJ
AF:
0.654
Gnomad4 EAS
AF:
0.835
Gnomad4 SAS
AF:
0.818
Gnomad4 FIN
AF:
0.532
Gnomad4 NFE
AF:
0.647
Gnomad4 OTH
AF:
0.721
Alfa
AF:
0.665
Hom.:
63874
Bravo
AF:
0.735
Asia WGS
AF:
0.812
AC:
2822
AN:
3478
EpiCase
AF:
0.656
EpiControl
AF:
0.654

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
Cadd
Benign
0.88
Dann
Benign
0.78
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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.

Other links and lift over

dbSNP: rs887854; hg19: chr16-5075542; COSMIC: COSV56570361; COSMIC: COSV56570361; API