NM_000642.3:c.2955T>C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_000642.3(AGL):c.2955T>C(p.Gly985Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. G985G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

AGL
NM_000642.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.405

Publications

0 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: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 1-99891611-T-C is Benign according to our data. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-99891611-T-C is described in CliVar as Likely_benign. Clinvar id is 456480.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.405 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGL	NM_000642.3 link	c.2955T>C	p.Gly985Gly	synonymous_variant	Exon 23 of 34	ENST00000361915.8	NP_000633.2	P35573-1A0A0S2A4E4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGL	ENST00000361915.8 link	c.2955T>C	p.Gly985Gly	synonymous_variant	Exon 23 of 34	1	NM_000642.3	ENSP00000355106.3		P35573-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251280

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461332

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726982

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33452

American (AMR)

AF:

0.00

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39632

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111646

Other (OTH)

AF:

0.00

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74298

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000241

AC:

AN:

41442

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67976

Other (OTH)

AF:

0.00

AC:

AN:

2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Glycogen storage disease type III

Benign:1

Apr 15, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

2.6

(source)

DANN

Benign

0.33

PhyloP100

-0.41

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over