rs746194098
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_000152.5(GAA):c.1932C>T(p.Ala644=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,610,446 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 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000029 ( 0 hom. )
Consequence
GAA
NM_000152.5 synonymous
NM_000152.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -9.15
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
?
Variant 17-80112919-C-T is Benign according to our data. Variant chr17-80112919-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 387757.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-9.15 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GAA | NM_000152.5 | c.1932C>T | p.Ala644= | synonymous_variant | 14/20 | ENST00000302262.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GAA | ENST00000302262.8 | c.1932C>T | p.Ala644= | synonymous_variant | 14/20 | 1 | NM_000152.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152184Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000454 AC: 11AN: 242126Hom.: 0 AF XY: 0.0000380 AC XY: 5AN XY: 131706
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GnomAD4 exome AF: 0.0000288 AC: 42AN: 1458262Hom.: 0 Cov.: 33 AF XY: 0.0000262 AC XY: 19AN XY: 725066
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152184Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5AN XY: 74336
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 29, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Glycogen storage disease, type II Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2023 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 06, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at