Variant 4-177431700-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000027.4(AGA):c.*8T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000412 in 1,599,736 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0024 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

AGA
NM_000027.4 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 1.25

Variant links:

Genes affected

AGA (HGNC:318): (aspartylglucosaminidase) This gene encodes a member of the N-terminal nucleophile (Ntn) hydrolase family of proteins. The encoded preproprotein is proteolytically processed to generate alpha and beta chains that comprise the mature enzyme. This enzyme is involved in the catabolism of N-linked oligosaccharides of glycoproteins. It cleaves asparagine from N-acetylglucosamines as one of the final steps in the lysosomal breakdown of glycoproteins. Mutations in this gene are associated with the lysosomal storage disease aspartylglycosaminuria that results in progressive neurodegeneration. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is subject to proteolytic processing. [provided by RefSeq, Nov 2015]

AGA links:

AGA (HGNC:):

AGA links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
AGA	NM_000027.4 linkuse as main transcript	c.*8T>C	3_prime_UTR_variant	9/9	ENST00000264595.7	NP_000018.2	P20933
AGA	NM_001171988.2 linkuse as main transcript	c.*8T>C	3_prime_UTR_variant	9/9		NP_001165459.1	P20933
AGA	NR_033655.2 linkuse as main transcript	n.1035T>C	non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGA	ENST00000264595 linkuse as main transcript	c.*8T>C		3_prime_UTR_variant	9/9	1	NM_000027.4	ENSP00000264595.2		P20933

Frequencies

GnomAD3 genomes

AF:

0.00237

AC:

360

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00833

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000594

AC:

149

AN:

250760

Hom.:

AF XY:

0.000465

AC XY:

AN XY:

135572

show subpopulations

Gnomad AFR exome

AF:

0.00864

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000207

AC:

299

AN:

1447436

Hom.:

Cov.:

AF XY:

0.000178

AC XY:

128

AN XY:

721014

show subpopulations

Gnomad4 AFR exome

AF:

0.00765

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000699

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.10e-7

Gnomad4 OTH exome

AF:

0.000500

GnomAD4 genome

AF:

0.00236

AC:

360

AN:

152300

Hom.:

Cov.:

AF XY:

0.00256

AC XY:

191

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00830

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00112

Hom.:

Bravo

AF:

0.00259

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Aspartylglucosaminuria

Uncertain:2

Uncertain significance, no assertion criteria provided	clinical testing	Natera, Inc.	Apr 16, 2020	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

9.4

DANN

Benign

0.83

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