Genetic Variant AGL:p.Glu814Gly (chr1-99884346-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000361915.8(AGL):c.2441A>G(p.Glu814Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E814A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

AGL
ENST00000361915.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.86

Publications

1 publications found

Variant links:

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

AGL links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33064184).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361915.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
AGL	NM_000642.3	MANE Select	c.2441A>G	p.Glu814Gly	missense	Exon 19 of 34	NP_000633.2
AGL	NM_000028.3		c.2441A>G	p.Glu814Gly	missense	Exon 19 of 34	NP_000019.2
AGL	NM_000643.3		c.2441A>G	p.Glu814Gly	missense	Exon 19 of 34	NP_000634.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
AGL	ENST00000361915.8	TSL:1 MANE Select	c.2441A>G	p.Glu814Gly	missense	Exon 19 of 34	ENSP00000355106.3
AGL	ENST00000294724.8	TSL:1	c.2441A>G	p.Glu814Gly	missense	Exon 19 of 34	ENSP00000294724.4
AGL	ENST00000370163.7	TSL:1	c.2441A>G	p.Glu814Gly	missense	Exon 19 of 34	ENSP00000359182.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.80

M_CAP

Benign

0.015

MetaRNN

Benign

0.33

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PhyloP100

8.9

PrimateAI

Benign

0.42

PROVEAN

Benign

-2.3

REVEL

Benign

0.17

Sift

Benign

0.069

Sift4G

Benign

0.31

Polyphen

0.0060

Vest4

0.38

MutPred

0.46

Gain of MoRF binding (P = 0.0312)

MVP

0.55

MPC

0.050

ClinPred

0.87

GERP RS

5.8

Varity_R

0.24

gMVP

0.54

Mutation Taster

=52/48

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over