rs150343359

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7

The NM_000152.5(GAA):c.915G>A(p.Gly305Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00125 in 1,612,034 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. G305G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 0 hom. )

Consequence

GAA
NM_000152.5 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:8

Conservation

PhyloP100: -2.28

Publications

8 publications found

Variant links:

Genes affected

GAA (HGNC:4065): (alpha glucosidase) This gene encodes lysosomal alpha-glucosidase, which is essential for the degradation of glycogen to glucose in lysosomes. The encoded preproprotein is proteolytically processed to generate multiple intermediate forms and the mature form of the enzyme. Defects in this gene are the cause of glycogen storage disease II, also known as Pompe's disease, which is an autosomal recessive disorder with a broad clinical spectrum. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

GAA Gene-Disease associations (from GenCC):

glycogen storage disease II
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), G2P, Laboratory for Molecular Medicine
glycogen storage disease due to acid maltase deficiency, infantile onset
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
glycogen storage disease due to acid maltase deficiency, late-onset
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

GAA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 17-80107856-G-A is Benign according to our data. Variant chr17-80107856-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 188478.

BP7

Synonymous conserved (PhyloP=-2.28 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000152.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GAA	NM_000152.5	MANE Select	c.915G>A	p.Gly305Gly	synonymous	Exon 5 of 20	NP_000143.2	P10253
GAA	NM_001079803.3		c.915G>A	p.Gly305Gly	synonymous	Exon 6 of 21	NP_001073271.1	P10253
GAA	NM_001079804.3		c.915G>A	p.Gly305Gly	synonymous	Exon 5 of 20	NP_001073272.1	P10253

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GAA	ENST00000302262.8	TSL:1 MANE Select	c.915G>A	p.Gly305Gly	synonymous	Exon 5 of 20	ENSP00000305692.3	P10253
GAA	ENST00000390015.7	TSL:1	c.915G>A	p.Gly305Gly	synonymous	Exon 6 of 21	ENSP00000374665.3	P10253
GAA	ENST00000933406.1		c.915G>A	p.Gly305Gly	synonymous	Exon 5 of 20	ENSP00000603465.1

Frequencies

GnomAD3 genomes

AF:

0.00108

AC:

164

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00184

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00112

AC:

275

AN:

245568

AF XY:

0.00117

show subpopulations

Gnomad AFR exome

AF:

0.000383

Gnomad AMR exome

AF:

0.00117

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00187

Gnomad OTH exome

AF:

0.00101

GnomAD4 exome

AF:

0.00127

AC:

1856

AN:

1459706

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

959

AN XY:

726150

show subpopulations

African (AFR)

AF:

0.000269

AC:

AN:

33452

American (AMR)

AF:

0.00150

AC:

AN:

44642

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.000464

AC:

AN:

86174

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52172

Middle Eastern (MID)

AF:

0.00293

AC:

AN:

5464

European-Non Finnish (NFE)

AF:

0.00149

AC:

1652

AN:

1111752

Other (OTH)

AF:

0.00118

AC:

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

117

234

351

468

585

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00108

AC:

164

AN:

152328

Hom.:

Cov.:

AF XY:

0.000926

AC XY:

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.000457

AC:

AN:

41568

American (AMR)

AF:

0.000784

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00184

AC:

125

AN:

68022

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00125

Hom.:

Bravo

AF:

0.00115

EpiCase

AF:

0.00224

EpiControl

AF:

0.00178

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Glycogen storage disease, type II (6)

not provided (4)

Cardiovascular phenotype (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

4.9

(source)

DANN

Benign

0.72

PhyloP100

-2.3

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over