Variant 4-177431525-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_000027.4(AGA):c.*183A>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 0.586 in 659,422 control chromosomes in the GnomAD database, including 118,338 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 22262 hom., cov: 33)

Exomes 𝑓: 0.61 ( 96076 hom. )

Consequence

AGA
NM_000027.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.32

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 4-177431525-T-G is Benign according to our data. Variant chr4-177431525-T-G is described in ClinVar as [Benign]. Clinvar id is 348224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
AGA	NM_000027.4 linkuse as main transcript	c.*183A>C	3_prime_UTR_variant	9/9	ENST00000264595.7
AGA	NM_001171988.2 linkuse as main transcript	c.*183A>C	3_prime_UTR_variant	9/9
AGA	NR_033655.2 linkuse as main transcript	n.1210A>C	non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGA	ENST00000264595.7 linkuse as main transcript	c.*183A>C		3_prime_UTR_variant	9/9	1	NM_000027.4	P1

Frequencies

GnomAD3 genomes

AF:

0.512

AC:

77781

AN:

151814

Hom.:

22256

Cov.:

show subpopulations

Gnomad AFR

AF:

0.254

Gnomad AMI

AF:

0.711

Gnomad AMR

AF:

0.479

Gnomad ASJ

AF:

0.573

Gnomad EAS

AF:

0.484

Gnomad SAS

AF:

0.570

Gnomad FIN

AF:

0.532

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.665

Gnomad OTH

AF:

0.543

GnomAD3 exomes

AF:

0.573

AC:

69635

AN:

121612

Hom.:

20736

AF XY:

0.579

AC XY:

37654

AN XY:

65060

show subpopulations

Gnomad AFR exome

AF:

0.248

Gnomad AMR exome

AF:

0.483

Gnomad ASJ exome

AF:

0.577

Gnomad EAS exome

AF:

0.496

Gnomad SAS exome

AF:

0.572

Gnomad FIN exome

AF:

0.544

Gnomad NFE exome

AF:

0.666

Gnomad OTH exome

AF:

0.582

GnomAD4 exome

AF:

0.608

AC:

308347

AN:

507490

Hom.:

96076

Cov.:

AF XY:

0.610

AC XY:

167853

AN XY:

275050

show subpopulations

Gnomad4 AFR exome

AF:

0.250

Gnomad4 AMR exome

AF:

0.489

Gnomad4 ASJ exome

AF:

0.573

Gnomad4 EAS exome

AF:

0.484

Gnomad4 SAS exome

AF:

0.579

Gnomad4 FIN exome

AF:

0.555

Gnomad4 NFE exome

AF:

0.664

Gnomad4 OTH exome

AF:

0.583

GnomAD4 genome

AF:

0.512

AC:

77800

AN:

151932

Hom.:

22262

Cov.:

AF XY:

0.505

AC XY:

37509

AN XY:

74244

show subpopulations

Gnomad4 AFR

AF:

0.253

Gnomad4 AMR

AF:

0.479

Gnomad4 ASJ

AF:

0.573

Gnomad4 EAS

AF:

0.483

Gnomad4 SAS

AF:

0.571

Gnomad4 FIN

AF:

0.532

Gnomad4 NFE

AF:

0.665

Gnomad4 OTH

AF:

0.547

Alfa

AF:

0.579

Hom.:

5868

Bravo

AF:

0.496

Asia WGS

AF:

0.460

AC:

1598

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

- -

Aspartylglucosaminuria

Benign:1

Benign, 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

-0.39

CADD

Benign

7.3

DANN

Benign

0.85

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