rs17121644

Variant names:

• chr1-99919874-C-T
• rs17121644
• NM_000642.3:c.4482-1660C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000642.3(AGL):​c.4482-1660C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0521 in 152,234 control chromosomes in the GnomAD database, including 256 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.052 (256 hom., cov: 32)
• Consequence: AGL NM_000642.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.652
• Publications: 1 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

ENSG00000288826 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGL	NM_000642.3	c.4482-1660C>T		intron_variant	Intron 33 of 33	ENST00000361915.8	NP_000633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGL	ENST00000361915.8	c.4482-1660C>T		intron_variant	Intron 33 of 33	1	NM_000642.3	ENSP00000355106.3

Frequencies

GnomAD3 genomes AF: 0.0521 AC: 7930 AN: 152116 Hom.: 256 Cov.: 32

Gnomad AFR AF: 0.0794

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0303

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.0154

Gnomad SAS AF: 0.0460

Gnomad FIN AF: 0.0558

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0457

Gnomad OTH AF: 0.0446

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0521 AC: 7928 AN: 152234 Hom.: 256 Cov.: 32 AF XY: 0.0513 AC XY: 3818 AN XY: 74446

African (AFR) AF: 0.0793 AC: 3294 AN: 41526

American (AMR) AF: 0.0302 AC: 462 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00922 AC: 32 AN: 3472

East Asian (EAS) AF: 0.0155 AC: 80 AN: 5168

South Asian (SAS) AF: 0.0454 AC: 219 AN: 4826

European-Finnish (FIN) AF: 0.0558 AC: 593 AN: 10618

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0457 AC: 3110 AN: 68010

Other (OTH) AF: 0.0432 AC: 91 AN: 2106

Alfa AF: 0.0427 Hom.: 227

Bravo AF: 0.0486

Asia WGS AF: 0.0280 AC: 97 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.47
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17121644; hg19: chr1-100385430;