Variant rs2035961 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.2950-21T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 1,611,376 control chromosomes in the GnomAD database, including 232,599 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 18798 hom., cov: 31)

Exomes 𝑓: 0.54 ( 213801 hom. )

Consequence

AGL
NM_000642.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0910

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=-0.8).

BP6

Variant 1-99891585-T-A is Benign according to our data. Variant chr1-99891585-T-A is described in ClinVar as [Benign]. Clinvar id is 256733.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.656 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.2950-21T>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.2950-21T>A		intron_variant		1	NM_000642.3	ENSP00000355106	P1	P35573-1

Frequencies

GnomAD3 genomes

AF:

0.489

AC:

74232

AN:

151708

Hom.:

18763

Cov.:

show subpopulations

Gnomad AFR

AF:

0.376

Gnomad AMI

AF:

0.464

Gnomad AMR

AF:

0.545

Gnomad ASJ

AF:

0.388

Gnomad EAS

AF:

0.675

Gnomad SAS

AF:

0.593

Gnomad FIN

AF:

0.485

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.531

Gnomad OTH

AF:

0.487

GnomAD3 exomes

AF:

0.537

AC:

134648

AN:

250876

Hom.:

36969

AF XY:

0.537

AC XY:

72825

AN XY:

135622

show subpopulations

Gnomad AFR exome

AF:

0.380

Gnomad AMR exome

AF:

0.613

Gnomad ASJ exome

AF:

0.395

Gnomad EAS exome

AF:

0.659

Gnomad SAS exome

AF:

0.585

Gnomad FIN exome

AF:

0.479

Gnomad NFE exome

AF:

0.527

Gnomad OTH exome

AF:

0.519

GnomAD4 exome

AF:

0.538

AC:

785552

AN:

1459550

Hom.:

213801

Cov.:

AF XY:

0.538

AC XY:

391027

AN XY:

726170

show subpopulations

Gnomad4 AFR exome

AF:

0.370

Gnomad4 AMR exome

AF:

0.602

Gnomad4 ASJ exome

AF:

0.403

Gnomad4 EAS exome

AF:

0.676

Gnomad4 SAS exome

AF:

0.585

Gnomad4 FIN exome

AF:

0.488

Gnomad4 NFE exome

AF:

0.540

Gnomad4 OTH exome

AF:

0.517

GnomAD4 genome

AF:

0.489

AC:

74307

AN:

151826

Hom.:

18798

Cov.:

AF XY:

0.491

AC XY:

36454

AN XY:

74212

show subpopulations

Gnomad4 AFR

AF:

0.376

Gnomad4 AMR

AF:

0.546

Gnomad4 ASJ

AF:

0.388

Gnomad4 EAS

AF:

0.674

Gnomad4 SAS

AF:

0.594

Gnomad4 FIN

AF:

0.485

Gnomad4 NFE

AF:

0.532

Gnomad4 OTH

AF:

0.494

Alfa

AF:

0.499

Hom.:

3540

Bravo

AF:

0.490

Asia WGS

AF:

0.626

AC:

2176

AN:

3476

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

-0.80

CADD

Benign

5.5

DANN

Benign

0.51

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