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.
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
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.
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.0000241
AC:
1
AN:
41442
American (AMR)
AF:
0.00
AC:
0
AN:
15264
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3464
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5198
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4836
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10596
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67976
Other (OTH)
AF:
0.00
AC:
0
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.