rs121907941

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PS1_ModeratePM2PP5

The NM_000152.5(GAA):​c.1585_1586delTCinsGT​(p.Ser529Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely pathogenic in UniProt.

Frequency

Genomes: not found (cov: 33)

Consequence

GAA
NM_000152.5 missense

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 4.92
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PS1
Transcript NM_000152.5 (GAA) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 17-80110974-TC-GT is Pathogenic according to our data. Variant chr17-80110974-TC-GT is described in ClinVar as [Pathogenic]. Clinvar id is 4026.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GAANM_000152.5 linkc.1585_1586delTCinsGT p.Ser529Val missense_variant ENST00000302262.8 NP_000143.2 P10253

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GAAENST00000302262.8 linkc.1585_1586delTCinsGT p.Ser529Val missense_variant 1 NM_000152.5 ENSP00000305692.3 P10253

Frequencies

GnomAD3 genomes
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

GLYCOGEN STORAGE DISEASE II, ADULT FORM Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMApr 01, 1996- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs121907941; hg19: chr17-78084773; API