rs2307130

Variant names:

• chr1-99851033-A-G
• rs2307130
• NM_000642.3:c.-10A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-99851033-A-G
• chr1-99851033-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000642.3(AGL):​c.-10A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 1,610,628 control chromosomes in the GnomAD database, including 191,964 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (14097 hom., cov: 33)
  • Exomes 𝑓: 0.49 (177867 hom.)
• Consequence: AGL NM_000642.3 5_prime_UTR_premature_start_codon_gain
• Scores: Splicing: ADA: 0.0001780
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.357
• Publications: 34 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: Ambry Genetics, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Laboratory for Molecular Medicine, Myriad Women’s Health

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 1-99851033-A-G is Benign according to our data. Variant chr1-99851033-A-G is described in ClinVar as Benign. ClinVar VariationId is 195096.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.528 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGL	NM_000642.3	MANE Select	c.-10A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 34	NP_000633.2	P35573-1
	AGL	NM_000642.3	MANE Select	c.-10A>G		5_prime_UTR	Exon 2 of 34	NP_000633.2	P35573-1
	AGL	NM_000028.3		c.-10A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 34	NP_000019.2	P35573-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGL	ENST00000361915.8	TSL:1 MANE Select	c.-10A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 34	ENSP00000355106.3	P35573-1
	AGL	ENST00000294724.8	TSL:1	c.-10A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 34	ENSP00000294724.4	P35573-1
	AGL	ENST00000370163.7	TSL:1	c.-10A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 34	ENSP00000359182.3	P35573-1

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63647 AN: 151976 Hom.: 14073 Cov.: 33

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.422

GnomAD2 exomes AF: 0.469 AC: 117972 AN: 251340 AF XY: 0.479

Gnomad AFR exome AF: 0.263

Gnomad AMR exome AF: 0.439

Gnomad ASJ exome AF: 0.390

Gnomad EAS exome AF: 0.534

Gnomad FIN exome AF: 0.437

Gnomad NFE exome AF: 0.492

Gnomad OTH exome AF: 0.469

GnomAD4 exome AF: 0.491 AC: 715475 AN: 1458534 Hom.: 177867 Cov.: 31 AF XY: 0.493 AC XY: 357476 AN XY: 725786

African (AFR) AF: 0.258 AC: 8622 AN: 33382

American (AMR) AF: 0.435 AC: 19460 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 10404 AN: 26114

East Asian (EAS) AF: 0.545 AC: 21611 AN: 39632

South Asian (SAS) AF: 0.538 AC: 46346 AN: 86202

European-Finnish (FIN) AF: 0.443 AC: 23680 AN: 53400

Middle Eastern (MID) AF: 0.371 AC: 2130 AN: 5740

European-Non Finnish (NFE) AF: 0.500 AC: 554774 AN: 1109108

Other (OTH) AF: 0.472 AC: 28448 AN: 60244

GnomAD4 genome AF: 0.419 AC: 63701 AN: 152094 Hom.: 14097 Cov.: 33 AF XY: 0.420 AC XY: 31205 AN XY: 74338

African (AFR) AF: 0.263 AC: 10915 AN: 41496

American (AMR) AF: 0.435 AC: 6646 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1370 AN: 3472

East Asian (EAS) AF: 0.545 AC: 2814 AN: 5166

South Asian (SAS) AF: 0.545 AC: 2628 AN: 4824

European-Finnish (FIN) AF: 0.434 AC: 4579 AN: 10558

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.490 AC: 33328 AN: 67974

Other (OTH) AF: 0.431 AC: 910 AN: 2110

Alfa AF: 0.459 Hom.: 50876

Bravo AF: 0.413

Asia WGS AF: 0.530 AC: 1845 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Glycogen storage disease type III (4)
-	-	3	not specified (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.82
PhyloP100		0.36
Mutation Taster		=46/54	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00018
dbscSNV1_RF	Benign	0.0
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: rs2307130; hg19: chr1-100316589; COSMIC: COSV54056176; COSMIC: COSV54056176;