rs563472929

Variant names:

• chr1-99877819-C-T
• rs563472929
• NM_000642.3:c.1602C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-99877819-C-T
• chr1-99877819-C-A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS1

The NM_000642.3(AGL):​c.1602C>T​(p.His534His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000126 in 1,613,892 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 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: AGL NM_000642.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.145
• Publications: 0 publications found

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: Ambry Genetics, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Laboratory for Molecular Medicine, Myriad Women’s Health

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 1-99877819-C-T is Benign according to our data. Variant chr1-99877819-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 456456.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.145 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.00013 (190/1461588) while in subpopulation AMR AF = 0.00309 (138/44716). AF 95% confidence interval is 0.00267. There are 0 homozygotes in GnomAdExome4. There are 82 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000642.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGL	NM_000642.3	MANE Select	c.1602C>T	p.His534His	synonymous	Exon 12 of 34	NP_000633.2	P35573-1
	AGL	NM_000028.3		c.1602C>T	p.His534His	synonymous	Exon 12 of 34	NP_000019.2	P35573-1
	AGL	NM_000643.3		c.1602C>T	p.His534His	synonymous	Exon 12 of 34	NP_000634.2	A0A0S2A4E4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGL	ENST00000361915.8	TSL:1 MANE Select	c.1602C>T	p.His534His	synonymous	Exon 12 of 34	ENSP00000355106.3	P35573-1
	AGL	ENST00000294724.8	TSL:1	c.1602C>T	p.His534His	synonymous	Exon 12 of 34	ENSP00000294724.4	P35573-1
	AGL	ENST00000370163.7	TSL:1	c.1602C>T	p.His534His	synonymous	Exon 12 of 34	ENSP00000359182.3	P35573-1

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000610 AC: 153 AN: 250986 AF XY: 0.000457

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00353

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000130 AC: 190 AN: 1461588 Hom.: 0 Cov.: 32 AF XY: 0.000113 AC XY: 82 AN XY: 727096

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00309 AC: 138 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39658

South Asian (SAS) AF: 0.000359 AC: 31 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1111838

Other (OTH) AF: 0.000132 AC: 8 AN: 60382

GnomAD4 genome AF: 0.0000919 AC: 14 AN: 152304 Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7 AN XY: 74470

African (AFR) AF: 0.0000481 AC: 2 AN: 41570

American (AMR) AF: 0.000457 AC: 7 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68024

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000212

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Glycogen storage disease type III (3)
-	-	1	AGL-related disorder (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	6.7
DANN	Benign	0.69
PhyloP100		-0.14
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs563472929; hg19: chr1-100343375;