Variant rs71402581 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_016256.4(NAGPA):c.1175-22_1175-16del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 1,608,326 control chromosomes in the GnomAD database, including 138,732 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.39 ( 11732 hom., cov: 0)

Exomes 𝑓: 0.41 ( 127000 hom. )

Consequence

NAGPA
NM_016256.4 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.20

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 16-5027394-TGGGAGGA-T is Benign according to our data. Variant chr16-5027394-TGGGAGGA-T is described in ClinVar as [Likely_benign]. Clinvar id is 260703.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAGPA	NM_016256.4 linkuse as main transcript	c.1175-22_1175-16del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000312251.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAGPA	ENST00000312251.8 linkuse as main transcript	c.1175-22_1175-16del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_016256.4	P1	Q9UK23-1

Frequencies

GnomAD3 genomes

AF:

0.393

AC:

59455

AN:

151294

Hom.:

11716

Cov.:

show subpopulations

Gnomad AFR

AF:

0.376

Gnomad AMI

AF:

0.381

Gnomad AMR

AF:

0.329

Gnomad ASJ

AF:

0.448

Gnomad EAS

AF:

0.345

Gnomad SAS

AF:

0.395

Gnomad FIN

AF:

0.344

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.424

Gnomad OTH

AF:

0.428

GnomAD3 exomes

AF:

0.382

AC:

94151

AN:

246258

Hom.:

18337

AF XY:

0.392

AC XY:

52433

AN XY:

133880

show subpopulations

Gnomad AFR exome

AF:

0.369

Gnomad AMR exome

AF:

0.261

Gnomad ASJ exome

AF:

0.459

Gnomad EAS exome

AF:

0.345

Gnomad SAS exome

AF:

0.412

Gnomad FIN exome

AF:

0.348

Gnomad NFE exome

AF:

0.418

Gnomad OTH exome

AF:

0.413

GnomAD4 exome

AF:

0.414

AC:

603491

AN:

1456908

Hom.:

127000

AF XY:

0.416

AC XY:

301830

AN XY:

724976

show subpopulations

Gnomad4 AFR exome

AF:

0.371

Gnomad4 AMR exome

AF:

0.269

Gnomad4 ASJ exome

AF:

0.459

Gnomad4 EAS exome

AF:

0.357

Gnomad4 SAS exome

AF:

0.416

Gnomad4 FIN exome

AF:

0.353

Gnomad4 NFE exome

AF:

0.424

Gnomad4 OTH exome

AF:

0.421

GnomAD4 genome

AF:

0.393

AC:

59505

AN:

151418

Hom.:

11732

Cov.:

AF XY:

0.389

AC XY:

28763

AN XY:

73956

show subpopulations

Gnomad4 AFR

AF:

0.376

Gnomad4 AMR

AF:

0.328

Gnomad4 ASJ

AF:

0.448

Gnomad4 EAS

AF:

0.345

Gnomad4 SAS

AF:

0.397

Gnomad4 FIN

AF:

0.344

Gnomad4 NFE

AF:

0.424

Gnomad4 OTH

AF:

0.423

Alfa

AF:

0.304

Hom.:

1185

Bravo

AF:

0.393

Asia WGS

AF:

0.323

AC:

1123

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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