rs143885684

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 2P and 15B. PM2BP4_ModerateBP6_Very_StrongBP7BS1

The NM_000642.3(AGL):​c.3822C>T​(p.Ile1274Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000093 in 1,612,776 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 (★★).

Frequency

Genomes: 𝑓 0.00048 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

AGL
NM_000642.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.620
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.27).
BP6
Variant 1-99910833-C-T is Benign according to our data. Variant chr1-99910833-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 384995.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.62 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00048 (73/152180) while in subpopulation AFR AF= 0.00168 (70/41544). AF 95% confidence interval is 0.00137. There are 0 homozygotes in gnomad4. There are 28 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AGLNM_000642.3 linkc.3822C>T p.Ile1274Ile synonymous_variant Exon 28 of 34 ENST00000361915.8 NP_000633.2 P35573-1A0A0S2A4E4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AGLENST00000361915.8 linkc.3822C>T p.Ile1274Ile synonymous_variant Exon 28 of 34 1 NM_000642.3 ENSP00000355106.3 P35573-1

Frequencies

GnomAD3 genomes
AF:
0.000480
AC:
73
AN:
152066
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000957
GnomAD3 exomes
AF:
0.000116
AC:
29
AN:
250304
Hom.:
0
AF XY:
0.0000591
AC XY:
8
AN XY:
135272
show subpopulations
Gnomad AFR exome
AF:
0.00173
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000527
AC:
77
AN:
1460596
Hom.:
0
Cov.:
30
AF XY:
0.0000633
AC XY:
46
AN XY:
726576
show subpopulations
Gnomad4 AFR exome
AF:
0.00200
Gnomad4 AMR exome
AF:
0.0000672
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000829
GnomAD4 genome
AF:
0.000480
AC:
73
AN:
152180
Hom.:
0
Cov.:
32
AF XY:
0.000376
AC XY:
28
AN XY:
74410
show subpopulations
Gnomad4 AFR
AF:
0.00168
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000947
Alfa
AF:
0.000747
Hom.:
0
Bravo
AF:
0.000665

ClinVar

Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Glycogen storage disease type III Benign:2
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 29, 2025- -
Likely benign, criteria provided, single submitterclinical testingGenome-Nilou LabApr 11, 2023- -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxApr 17, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.27
CADD
Benign
7.1
DANN
Benign
0.77
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

LitVar

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

Other links and lift over

dbSNP: rs143885684; hg19: chr1-100376389; COSMIC: COSV104592651; API