rs548255

Variant names:

• chr1-99900897-T-G
• rs548255
• NM_000642.3:c.3588+36T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-99900897-T-G
• chr1-99900897-T-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000642.3(AGL):​c.3588+36T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 1,519,308 control chromosomes in the GnomAD database, including 276 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (44 hom., cov: 30)
  • Exomes 𝑓: 0.014 (232 hom.)
• Consequence: AGL NM_000642.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.305
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-99900897-T-G is Benign according to our data. Variant chr1-99900897-T-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 256740.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0192 (2912/151966) while in subpopulation AFR AF = 0.0252 (1047/41476). AF 95% confidence interval is 0.024. There are 44 homozygotes in GnomAd4. There are 1426 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 44 AR gene

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.3588+36T>G		intron	N/A	NP_000633.2	P35573-1
	AGL	NM_000028.3		c.3588+36T>G		intron	N/A	NP_000019.2	P35573-1
	AGL	NM_000643.3		c.3588+36T>G		intron	N/A	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.3588+36T>G		intron	N/A	ENSP00000355106.3	P35573-1
	AGL	ENST00000294724.8	TSL:1	c.3588+36T>G		intron	N/A	ENSP00000294724.4	P35573-1
	AGL	ENST00000370163.7	TSL:1	c.3588+36T>G		intron	N/A	ENSP00000359182.3	P35573-1

Frequencies

GnomAD3 genomes AF: 0.0192 AC: 2917 AN: 151848 Hom.: 45 Cov.: 30

Gnomad AFR AF: 0.0253

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0159

Gnomad ASJ AF: 0.0294

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00477

Gnomad FIN AF: 0.0364

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0153

Gnomad OTH AF: 0.0249

GnomAD2 exomes AF: 0.0160 AC: 3695 AN: 230674 AF XY: 0.0158

Gnomad AFR exome AF: 0.0258

Gnomad AMR exome AF: 0.00779

Gnomad ASJ exome AF: 0.0294

Gnomad EAS exome AF: 0.0000591

Gnomad FIN exome AF: 0.0349

Gnomad NFE exome AF: 0.0171

Gnomad OTH exome AF: 0.0218

GnomAD4 exome AF: 0.0135 AC: 18495 AN: 1367342 Hom.: 232 Cov.: 24 AF XY: 0.0135 AC XY: 9240 AN XY: 683938

African (AFR) AF: 0.0266 AC: 811 AN: 30538

American (AMR) AF: 0.00850 AC: 351 AN: 41304

Ashkenazi Jewish (ASJ) AF: 0.0292 AC: 736 AN: 25248

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39218

South Asian (SAS) AF: 0.00484 AC: 383 AN: 79184

European-Finnish (FIN) AF: 0.0351 AC: 1811 AN: 51616

Middle Eastern (MID) AF: 0.0456 AC: 253 AN: 5554

European-Non Finnish (NFE) AF: 0.0127 AC: 13226 AN: 1037514

Other (OTH) AF: 0.0161 AC: 923 AN: 57166

GnomAD4 genome AF: 0.0192 AC: 2912 AN: 151966 Hom.: 44 Cov.: 30 AF XY: 0.0192 AC XY: 1426 AN XY: 74318

African (AFR) AF: 0.0252 AC: 1047 AN: 41476

American (AMR) AF: 0.0158 AC: 241 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0294 AC: 102 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00456 AC: 22 AN: 4820

European-Finnish (FIN) AF: 0.0364 AC: 381 AN: 10472

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0153 AC: 1041 AN: 67956

Other (OTH) AF: 0.0246 AC: 52 AN: 2112

Alfa AF: 0.0224 Hom.: 33

Bravo AF: 0.0175

Asia WGS AF: 0.00578 AC: 20 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Glycogen storage disease type III (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.37
DANN	Benign	0.14
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs548255; hg19: chr1-100366453;