1-99870805-C-T

Variant names:

• chr1-99870805-C-T
• rs2230306
• NM_000642.3:c.894C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_000642.3(AGL):​c.894C>T​(p.Leu298Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 1,609,158 control chromosomes in the GnomAD database, including 411,934 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (44477 hom., cov: 31)
  • Exomes 𝑓: 0.71 (367457 hom.)
• Consequence: AGL NM_000642.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 1.04
• Publications: 22 publications found

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 Gene-Disease associations (from GenCC):

• glycogen storage disease III

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, Laboratory for Molecular Medicine, Myriad Women’s Health, Orphanet, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 1-99870805-C-T is Benign according to our data. Variant chr1-99870805-C-T is described in ClinVar as Benign. ClinVar VariationId is 198432.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.04 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000642.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGL	NM_000642.3	MANE Select	c.894C>T	p.Leu298Leu	synonymous	Exon 7 of 34	NP_000633.2
	AGL	NM_000028.3		c.894C>T	p.Leu298Leu	synonymous	Exon 7 of 34	NP_000019.2
	AGL	NM_000643.3		c.894C>T	p.Leu298Leu	synonymous	Exon 7 of 34	NP_000634.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGL	ENST00000361915.8	TSL:1 MANE Select	c.894C>T	p.Leu298Leu	synonymous	Exon 7 of 34	ENSP00000355106.3
	AGL	ENST00000294724.8	TSL:1	c.894C>T	p.Leu298Leu	synonymous	Exon 7 of 34	ENSP00000294724.4
	AGL	ENST00000370163.7	TSL:1	c.894C>T	p.Leu298Leu	synonymous	Exon 7 of 34	ENSP00000359182.3

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115255 AN: 151898 Hom.: 44424 Cov.: 31

Gnomad AFR AF: 0.913

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.780

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.754

GnomAD2 exomes AF: 0.717 AC: 178869 AN: 249606 AF XY: 0.717

Gnomad AFR exome AF: 0.917

Gnomad AMR exome AF: 0.691

Gnomad ASJ exome AF: 0.693

Gnomad EAS exome AF: 0.685

Gnomad FIN exome AF: 0.673

Gnomad NFE exome AF: 0.703

Gnomad OTH exome AF: 0.722

GnomAD4 exome AF: 0.709 AC: 1032440 AN: 1457142 Hom.: 367457 Cov.: 41 AF XY: 0.709 AC XY: 514445 AN XY: 725154

African (AFR) AF: 0.921 AC: 30766 AN: 33404

American (AMR) AF: 0.690 AC: 30833 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.697 AC: 18172 AN: 26076

East Asian (EAS) AF: 0.696 AC: 27514 AN: 39534

South Asian (SAS) AF: 0.752 AC: 64760 AN: 86082

European-Finnish (FIN) AF: 0.682 AC: 36388 AN: 53392

Middle Eastern (MID) AF: 0.731 AC: 4205 AN: 5752

European-Non Finnish (NFE) AF: 0.701 AC: 776724 AN: 1108020

Other (OTH) AF: 0.715 AC: 43078 AN: 60212

GnomAD4 genome AF: 0.759 AC: 115370 AN: 152016 Hom.: 44477 Cov.: 31 AF XY: 0.758 AC XY: 56316 AN XY: 74270

African (AFR) AF: 0.913 AC: 37900 AN: 41516

American (AMR) AF: 0.716 AC: 10926 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2387 AN: 3470

East Asian (EAS) AF: 0.697 AC: 3601 AN: 5166

South Asian (SAS) AF: 0.763 AC: 3670 AN: 4812

European-Finnish (FIN) AF: 0.674 AC: 7099 AN: 10530

Middle Eastern (MID) AF: 0.767 AC: 224 AN: 292

European-Non Finnish (NFE) AF: 0.696 AC: 47315 AN: 67952

Other (OTH) AF: 0.759 AC: 1598 AN: 2106

Alfa AF: 0.724 Hom.: 30874

Bravo AF: 0.766

Asia WGS AF: 0.747 AC: 2589 AN: 3462

EpiCase AF: 0.703

EpiControl AF: 0.697

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	Glycogen storage disease type III (5)
-	-	3	not specified (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	7.0
DANN	Benign	0.79
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2230306; hg19: chr1-100336361; COSMIC: COSV108107726; COSMIC: COSV108107726;