Variant rs2291638 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.1424-44A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 1,577,868 control chromosomes in the GnomAD database, including 113,843 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 8133 hom., cov: 32)

Exomes 𝑓: 0.38 ( 105710 hom. )

Consequence

AGL
NM_000642.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.558

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=-0.68).

BP6

Variant 1-99877597-A-G is Benign according to our data. Variant chr1-99877597-A-G is described in ClinVar as [Benign]. Clinvar id is 256722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.444 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.1424-44A>G		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.1424-44A>G		intron_variant		1	NM_000642.3	ENSP00000355106	P1	P35573-1

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

45120

AN:

151976

Hom.:

8120

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0932

Gnomad AMI

AF:

0.335

Gnomad AMR

AF:

0.324

Gnomad ASJ

AF:

0.299

Gnomad EAS

AF:

0.460

Gnomad SAS

AF:

0.310

Gnomad FIN

AF:

0.346

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.393

Gnomad OTH

AF:

0.317

GnomAD3 exomes

AF:

0.351

AC:

86835

AN:

247060

Hom.:

16083

AF XY:

0.352

AC XY:

47131

AN XY:

133948

show subpopulations

Gnomad AFR exome

AF:

0.0899

Gnomad AMR exome

AF:

0.360

Gnomad ASJ exome

AF:

0.301

Gnomad EAS exome

AF:

0.445

Gnomad SAS exome

AF:

0.304

Gnomad FIN exome

AF:

0.345

Gnomad NFE exome

AF:

0.388

Gnomad OTH exome

AF:

0.363

GnomAD4 exome

AF:

0.379

AC:

540994

AN:

1425774

Hom.:

105710

Cov.:

AF XY:

0.377

AC XY:

268273

AN XY:

711422

show subpopulations

Gnomad4 AFR exome

AF:

0.0817

Gnomad4 AMR exome

AF:

0.355

Gnomad4 ASJ exome

AF:

0.311

Gnomad4 EAS exome

AF:

0.461

Gnomad4 SAS exome

AF:

0.305

Gnomad4 FIN exome

AF:

0.353

Gnomad4 NFE exome

AF:

0.397

Gnomad4 OTH exome

AF:

0.359

GnomAD4 genome

AF:

0.297

AC:

45152

AN:

152094

Hom.:

8133

Cov.:

AF XY:

0.296

AC XY:

21987

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.0932

Gnomad4 AMR

AF:

0.324

Gnomad4 ASJ

AF:

0.299

Gnomad4 EAS

AF:

0.459

Gnomad4 SAS

AF:

0.311

Gnomad4 FIN

AF:

0.346

Gnomad4 NFE

AF:

0.393

Gnomad4 OTH

AF:

0.325

Alfa

AF:

0.342

Hom.:

1812

Bravo

AF:

0.290

Asia WGS

AF:

0.366

AC:

1274

AN:

3478

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 23, 2018	- -
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

-0.68

CADD

Benign

9.1

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