Variant rs594249 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000642.3(AGL):c.3259+37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 1,589,346 control chromosomes in the GnomAD database, including 381,295 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33611 hom., cov: 33)

Exomes 𝑓: 0.69 ( 347684 hom. )

Consequence

AGL
NM_000642.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.87

Variant links:

Genes affected

AGL (HGNC:321): (amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase) This gene encodes the glycogen debrancher enzyme which is involved in glycogen degradation. This enzyme has two independent catalytic activities which occur at different sites on the protein: a 4-alpha-glucotransferase activity and a amylo-1,6-glucosidase activity. Mutations in this gene are associated with glycogen storage disease although a wide range of enzymatic and clinical variability occurs which may be due to tissue-specific alternative splicing. Alternatively spliced transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

AGL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 1-99892644-G-A is Benign according to our data. Variant chr1-99892644-G-A is described in ClinVar as [Benign]. Clinvar id is 256735.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGL	NM_000642.3 linkuse as main transcript	c.3259+37G>A		intron_variant		ENST00000361915.8	NP_000633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGL	ENST00000361915.8 linkuse as main transcript	c.3259+37G>A		intron_variant		1	NM_000642.3	ENSP00000355106	P1	P35573-1

Frequencies

GnomAD3 genomes

AF:

0.663

AC:

100673

AN:

151924

Hom.:

33579

Cov.:

show subpopulations

Gnomad AFR

AF:

0.582

Gnomad AMI

AF:

0.684

Gnomad AMR

AF:

0.695

Gnomad ASJ

AF:

0.601

Gnomad EAS

AF:

0.701

Gnomad SAS

AF:

0.749

Gnomad FIN

AF:

0.692

Gnomad MID

AF:

0.633

Gnomad NFE

AF:

0.694

Gnomad OTH

AF:

0.672

GnomAD3 exomes

AF:

0.691

AC:

171182

AN:

247704

Hom.:

59376

AF XY:

0.693

AC XY:

93065

AN XY:

134212

show subpopulations

Gnomad AFR exome

AF:

0.584

Gnomad AMR exome

AF:

0.723

Gnomad ASJ exome

AF:

0.614

Gnomad EAS exome

AF:

0.689

Gnomad SAS exome

AF:

0.735

Gnomad FIN exome

AF:

0.681

Gnomad NFE exome

AF:

0.694

Gnomad OTH exome

AF:

0.692

GnomAD4 exome

AF:

0.694

AC:

998176

AN:

1437304

Hom.:

347684

Cov.:

AF XY:

0.695

AC XY:

498117

AN XY:

716568

show subpopulations

Gnomad4 AFR exome

AF:

0.582

Gnomad4 AMR exome

AF:

0.719

Gnomad4 ASJ exome

AF:

0.618

Gnomad4 EAS exome

AF:

0.706

Gnomad4 SAS exome

AF:

0.734

Gnomad4 FIN exome

AF:

0.692

Gnomad4 NFE exome

AF:

0.696

Gnomad4 OTH exome

AF:

0.677

GnomAD4 genome

AF:

0.663

AC:

100749

AN:

152042

Hom.:

33611

Cov.:

AF XY:

0.665

AC XY:

49439

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.582

Gnomad4 AMR

AF:

0.695

Gnomad4 ASJ

AF:

0.601

Gnomad4 EAS

AF:

0.701

Gnomad4 SAS

AF:

0.749

Gnomad4 FIN

AF:

0.692

Gnomad4 NFE

AF:

0.694

Gnomad4 OTH

AF:

0.676

Alfa

AF:

0.682

Hom.:

18249

Bravo

AF:

0.656

Asia WGS

AF:

0.731

AC:

2540

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Glycogen storage disease type III

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.025

DANN

Benign

0.45

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