Variant rs834575 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.3700+32T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0455 in 1,507,456 control chromosomes in the GnomAD database, including 1,769 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 257 hom., cov: 32)

Exomes 𝑓: 0.045 ( 1512 hom. )

Consequence

AGL
NM_000642.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.243

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 1-99902826-T-C is Benign according to our data. Variant chr1-99902826-T-C is described in ClinVar as [Benign]. Clinvar id is 256742.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0774 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.3700+32T>C		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.3700+32T>C		intron_variant		1	NM_000642.3	ENSP00000355106	P1	P35573-1

Frequencies

GnomAD3 genomes

AF:

0.0522

AC:

7943

AN:

152152

Hom.:

257

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0797

Gnomad AMI

AF:

0.0482

Gnomad AMR

AF:

0.0301

Gnomad ASJ

AF:

0.00923

Gnomad EAS

AF:

0.0158

Gnomad SAS

AF:

0.0457

Gnomad FIN

AF:

0.0560

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0457

Gnomad OTH

AF:

0.0445

GnomAD3 exomes

AF:

0.0388

AC:

9382

AN:

241516

Hom.:

239

AF XY:

0.0389

AC XY:

5085

AN XY:

130828

show subpopulations

Gnomad AFR exome

AF:

0.0823

Gnomad AMR exome

AF:

0.0155

Gnomad ASJ exome

AF:

0.0103

Gnomad EAS exome

AF:

0.00496

Gnomad SAS exome

AF:

0.0446

Gnomad FIN exome

AF:

0.0536

Gnomad NFE exome

AF:

0.0436

Gnomad OTH exome

AF:

0.0365

GnomAD4 exome

AF:

0.0448

AC:

60647

AN:

1355186

Hom.:

1512

Cov.:

AF XY:

0.0445

AC XY:

30205

AN XY:

679508

show subpopulations

Gnomad4 AFR exome

AF:

0.0840

Gnomad4 AMR exome

AF:

0.0168

Gnomad4 ASJ exome

AF:

0.0117

Gnomad4 EAS exome

AF:

0.0313

Gnomad4 SAS exome

AF:

0.0441

Gnomad4 FIN exome

AF:

0.0535

Gnomad4 NFE exome

AF:

0.0460

Gnomad4 OTH exome

AF:

0.0407

GnomAD4 genome

AF:

0.0522

AC:

7941

AN:

152270

Hom.:

257

Cov.:

AF XY:

0.0514

AC XY:

3828

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0796

Gnomad4 AMR

AF:

0.0300

Gnomad4 ASJ

AF:

0.00923

Gnomad4 EAS

AF:

0.0158

Gnomad4 SAS

AF:

0.0452

Gnomad4 FIN

AF:

0.0560

Gnomad4 NFE

AF:

0.0457

Gnomad4 OTH

AF:

0.0430

Alfa

AF:

0.0465

Hom.:

Bravo

AF:

0.0486

Asia WGS

AF:

0.0280

AC:

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 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.2

DANN

Benign

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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