Variant rs115666491 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000642.3(AGL):c.1612-24C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 1,576,496 control chromosomes in the GnomAD database, including 182 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.013 ( 26 hom., cov: 32)

Exomes 𝑓: 0.013 ( 156 hom. )

Consequence

AGL
NM_000642.3 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.320

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:

AGL (HGNC:):

AGL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 2 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 1-99879899-C-A is Benign according to our data. Variant chr1-99879899-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 256724.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0127 (1929/152250) while in subpopulation NFE AF= 0.0153 (1038/68018). AF 95% confidence interval is 0.0145. There are 26 homozygotes in gnomad4. There are 983 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGL	NM_000642.3 linkuse as main transcript	c.1612-24C>A		intron_variant		ENST00000361915.8	NP_000633.2	P35573-1A0A0S2A4E4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGL	ENST00000361915.8 linkuse as main transcript	c.1612-24C>A		intron_variant		1	NM_000642.3	ENSP00000355106.3		P35573-1

Frequencies

GnomAD3 genomes

AF:

0.0127

AC:

1931

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00236

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0143

Gnomad ASJ

AF:

0.0294

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00436

Gnomad FIN

AF:

0.0361

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0153

Gnomad OTH

AF:

0.0210

GnomAD3 exomes

AF:

0.0135

AC:

3381

AN:

251130

Hom.:

AF XY:

0.0135

AC XY:

1836

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.00172

Gnomad AMR exome

AF:

0.00645

Gnomad ASJ exome

AF:

0.0286

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00363

Gnomad FIN exome

AF:

0.0338

Gnomad NFE exome

AF:

0.0166

Gnomad OTH exome

AF:

0.0194

GnomAD4 exome

AF:

0.0127

AC:

18057

AN:

1424246

Hom.:

156

Cov.:

AF XY:

0.0127

AC XY:

9059

AN XY:

710978

show subpopulations

Gnomad4 AFR exome

AF:

0.00300

Gnomad4 AMR exome

AF:

0.00737

Gnomad4 ASJ exome

AF:

0.0290

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00424

Gnomad4 FIN exome

AF:

0.0344

Gnomad4 NFE exome

AF:

0.0126

Gnomad4 OTH exome

AF:

0.0141

GnomAD4 genome

AF:

0.0127

AC:

1929

AN:

152250

Hom.:

Cov.:

AF XY:

0.0132

AC XY:

983

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00236

Gnomad4 AMR

AF:

0.0143

Gnomad4 ASJ

AF:

0.0294

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00436

Gnomad4 FIN

AF:

0.0361

Gnomad4 NFE

AF:

0.0153

Gnomad4 OTH

AF:

0.0208

Alfa

AF:

0.0189

Hom.:

Bravo

AF:

0.0102

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Mar 14, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 13, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Glycogen storage disease type III

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.7

DANN

Benign

0.52

BranchPoint Hunter

2.0

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.

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