rs2035961

chr1-99891585-T-Achr1-99891585-T-Cchr1-99891585-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0910

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]

ACMG classification

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	UniProt
AGL	NM_000642.3	c.2950-21T>A		intron_variant		ENST00000361915.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGL	ENST00000361915.8	c.2950-21T>A		intron_variant		1	NM_000642.3	P1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74232 AN: 151708 Hom.: 18763 Cov.: 31

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

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.: 40 AF XY: 0.538 AC XY: 391027 AN XY: 726170

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.: 31 AF XY: 0.491 AC XY: 36454 AN XY: 74212

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

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

Other links and lift over

dbSNP: rs2035961; hg19: chr1-100357141; COSMIC: COSV54051217;