NM_000152.5:c.69C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_000152.5(GAA):c.69C>T(p.Thr23Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,613,314 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 (★★). Synonymous variant affecting the same amino acid position (i.e. T23T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

GAA
NM_000152.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -4.89

Publications

6 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, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen, G2P
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: Benign. The variant received -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 17-80104655-C-T is Benign according to our data. Variant chr17-80104655-C-T is described in CliVar as Likely_benign. Clinvar id is 456431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80104655-C-T is described in CliVar as Likely_benign. Clinvar id is 456431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80104655-C-T is described in CliVar as Likely_benign. Clinvar id is 456431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80104655-C-T is described in CliVar as Likely_benign. Clinvar id is 456431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80104655-C-T is described in CliVar as Likely_benign. Clinvar id is 456431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80104655-C-T is described in CliVar as Likely_benign. Clinvar id is 456431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80104655-C-T is described in CliVar as Likely_benign. Clinvar id is 456431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80104655-C-T is described in CliVar as Likely_benign. Clinvar id is 456431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80104655-C-T is described in CliVar as Likely_benign. Clinvar id is 456431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80104655-C-T is described in CliVar as Likely_benign. Clinvar id is 456431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80104655-C-T is described in CliVar as Likely_benign. Clinvar id is 456431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80104655-C-T is described in CliVar as Likely_benign. Clinvar id is 456431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80104655-C-T is described in CliVar as Likely_benign. Clinvar id is 456431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80104655-C-T is described in CliVar as Likely_benign. Clinvar id is 456431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80104655-C-T is described in CliVar as Likely_benign. Clinvar id is 456431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80104655-C-T is described in CliVar as Likely_benign. Clinvar id is 456431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80104655-C-T is described in CliVar as Likely_benign. Clinvar id is 456431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80104655-C-T is described in CliVar as Likely_benign. Clinvar id is 456431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80104655-C-T is described in CliVar as Likely_benign. Clinvar id is 456431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.89 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAA	NM_000152.5 link	c.69C>T	p.Thr23Thr	synonymous_variant	Exon 2 of 20	ENST00000302262.8	NP_000143.2	P10253

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAA	ENST00000302262.8 link	c.69C>T	p.Thr23Thr	synonymous_variant	Exon 2 of 20	1	NM_000152.5	ENSP00000305692.3		P10253

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000240

AC:

AN:

250070

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1461026

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

726846

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.0000447

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52636

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000198

AC:

AN:

1111968

Other (OTH)

AF:

0.0000331

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152288

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41558

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.0000282

Hom.:

Bravo

AF:

0.0000189

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

GAA-related disorder

Benign:1

May 26, 2022

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Glycogen storage disease, type II

Benign:1

Jan 07, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.12

(source)

DANN

Benign

0.65

PhyloP100

-4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over