rs17121464

Positions:

chr1-99875231-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000361915.8(AGL):c.1160G>A(p.Arg387Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 1,613,966 control chromosomes in the GnomAD database, including 2,309 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 219 hom., cov: 33)

Exomes 𝑓: 0.019 ( 2090 hom. )

Consequence

AGL
ENST00000361915.8 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.70

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013240874).

BP6

Variant 1-99875231-G-A is Benign according to our data. Variant chr1-99875231-G-A is described in ClinVar as [Benign]. Clinvar id is 199034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-99875231-G-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGL	NM_000642.3 linkuse as main transcript	c.1160G>A	p.Arg387Gln	missense_variant	9/34	ENST00000361915.8	NP_000633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGL	ENST00000361915.8 linkuse as main transcript	c.1160G>A	p.Arg387Gln	missense_variant	9/34	1	NM_000642.3	ENSP00000355106	P1	P35573-1

Frequencies

GnomAD3 genomes

AF:

0.0208

AC:

3162

AN:

152160

Hom.:

217

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00357

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0712

Gnomad ASJ

AF:

0.00404

Gnomad EAS

AF:

0.184

Gnomad SAS

AF:

0.123

Gnomad FIN

AF:

0.0116

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00250

Gnomad OTH

AF:

0.0306

GnomAD3 exomes

AF:

0.0524

AC:

13144

AN:

250642

Hom.:

1085

AF XY:

0.0502

AC XY:

6808

AN XY:

135718

show subpopulations

Gnomad AFR exome

AF:

0.00340

Gnomad AMR exome

AF:

0.165

Gnomad ASJ exome

AF:

0.00427

Gnomad EAS exome

AF:

0.177

Gnomad SAS exome

AF:

0.112

Gnomad FIN exome

AF:

0.0100

Gnomad NFE exome

AF:

0.00190

Gnomad OTH exome

AF:

0.0366

GnomAD4 exome

AF:

0.0187

AC:

27344

AN:

1461688

Hom.:

2090

Cov.:

AF XY:

0.0207

AC XY:

15056

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.00272

Gnomad4 AMR exome

AF:

0.154

Gnomad4 ASJ exome

AF:

0.00486

Gnomad4 EAS exome

AF:

0.185

Gnomad4 SAS exome

AF:

0.110

Gnomad4 FIN exome

AF:

0.0106

Gnomad4 NFE exome

AF:

0.00126

Gnomad4 OTH exome

AF:

0.0233

GnomAD4 genome

AF:

0.0209

AC:

3176

AN:

152278

Hom.:

219

Cov.:

AF XY:

0.0245

AC XY:

1823

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00356

Gnomad4 AMR

AF:

0.0717

Gnomad4 ASJ

AF:

0.00404

Gnomad4 EAS

AF:

0.184

Gnomad4 SAS

AF:

0.124

Gnomad4 FIN

AF:

0.0116

Gnomad4 NFE

AF:

0.00250

Gnomad4 OTH

AF:

0.0326

Alfa

AF:

0.0118

Hom.:

273

Bravo

AF:

0.0266

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.0474

AC:

5752

Asia WGS

AF:

0.143

AC:

500

AN:

3478

EpiCase

AF:

0.00104

EpiControl

AF:

0.00178

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Glycogen storage disease type III

Benign:4

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 03, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 10, 2014	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 26, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

8.9

DANN

Benign

0.37

DEOGEN2

Benign

0.033

T;T;T;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.52

T;.;.;.;T

MetaRNN

Benign

0.0013

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

L;L;L;L;.

MutationTaster

Benign

1.0

P;P;P;P;P;P;P

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.29

N;N;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.85

T;T;T;T;T

Sift4G

Benign

0.59

T;T;T;T;T

Polyphen

0.0

B;B;B;B;B

Vest4

0.051

MPC

0.045

ClinPred

0.0015

GERP RS

-2.4

Varity_R

0.021

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over