Variant rs548255 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000642.3(AGL):c.3588+36T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 1,519,308 control chromosomes in the GnomAD database, including 276 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 44 hom., cov: 30)

Exomes 𝑓: 0.014 ( 232 hom. )

Consequence

AGL
NM_000642.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.305

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:

AGL (HGNC:):

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=-0.88).

BP6

Variant 1-99900897-T-G is Benign according to our data. Variant chr1-99900897-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 256740.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0192 (2912/151966) while in subpopulation AFR AF= 0.0252 (1047/41476). AF 95% confidence interval is 0.024. There are 44 homozygotes in gnomad4. There are 1426 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 44 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGL	NM_000642.3 linkuse as main transcript	c.3588+36T>G		intron_variant		ENST00000361915.8	NP_000633.2	P35573-1A0A0S2A4E4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGL	ENST00000361915.8 linkuse as main transcript	c.3588+36T>G		intron_variant		1	NM_000642.3	ENSP00000355106.3		P35573-1

Frequencies

GnomAD3 genomes

AF:

0.0192

AC:

2917

AN:

151848

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0253

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0159

Gnomad ASJ

AF:

0.0294

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00477

Gnomad FIN

AF:

0.0364

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0153

Gnomad OTH

AF:

0.0249

GnomAD3 exomes

AF:

0.0160

AC:

3695

AN:

230674

Hom.:

AF XY:

0.0158

AC XY:

1969

AN XY:

124846

show subpopulations

Gnomad AFR exome

AF:

0.0258

Gnomad AMR exome

AF:

0.00779

Gnomad ASJ exome

AF:

0.0294

Gnomad EAS exome

AF:

0.0000591

Gnomad SAS exome

AF:

0.00478

Gnomad FIN exome

AF:

0.0349

Gnomad NFE exome

AF:

0.0171

Gnomad OTH exome

AF:

0.0218

GnomAD4 exome

AF:

0.0135

AC:

18495

AN:

1367342

Hom.:

232

Cov.:

AF XY:

0.0135

AC XY:

9240

AN XY:

683938

show subpopulations

Gnomad4 AFR exome

AF:

0.0266

Gnomad4 AMR exome

AF:

0.00850

Gnomad4 ASJ exome

AF:

0.0292

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.00484

Gnomad4 FIN exome

AF:

0.0351

Gnomad4 NFE exome

AF:

0.0127

Gnomad4 OTH exome

AF:

0.0161

GnomAD4 genome

AF:

0.0192

AC:

2912

AN:

151966

Hom.:

Cov.:

AF XY:

0.0192

AC XY:

1426

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0252

Gnomad4 AMR

AF:

0.0158

Gnomad4 ASJ

AF:

0.0294

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.0364

Gnomad4 NFE

AF:

0.0153

Gnomad4 OTH

AF:

0.0246

Alfa

AF:

0.0224

Hom.:

Bravo

AF:

0.0175

Asia WGS

AF:

0.00578

AC:

AN:

3474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 29, 2019	- -

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

-0.88

CADD

Benign

0.37

DANN

Benign

0.14

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