rs834575

chr1-99902826-T-C

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.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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.243

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=-0.83).
• 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	UniProt
AGL	NM_000642.3	c.3700+32T>C		intron_variant		ENST00000361915.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGL	ENST00000361915.8	c.3700+32T>C		intron_variant		1	NM_000642.3	P1

Frequencies

GnomAD3 genomes AF: 0.0522 AC: 7943 AN: 152152 Hom.: 257 Cov.: 32

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

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.: 19 AF XY: 0.0445 AC XY: 30205 AN XY: 679508

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.: 32 AF XY: 0.0514 AC XY: 3828 AN XY: 74448

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.: 42

Bravo AF: 0.0486

Asia WGS AF: 0.0280 AC: 97 AN: 3478

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 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

Other links and lift over

dbSNP: rs834575; hg19: chr1-100368382;