rs1598564555

Variant names:

• chr17-80101820-G-A
• rs1598564555
• NM_000152.5:c.-103G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-80101820-G-A
• chr17-80101820-G-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_000152.5(GAA):​c.-103G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GAA NM_000152.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.648
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 17-80101820-G-A is Benign according to our data. Variant chr17-80101820-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 669043.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAA	NM_000152.5	MANE Select	c.-103G>A		5_prime_UTR	Exon 1 of 20	NP_000143.2	P10253
	GAA	NM_001079803.3		c.-103G>A		5_prime_UTR	Exon 2 of 21	NP_001073271.1	P10253
	GAA	NM_001406741.1		c.-103G>A		5_prime_UTR	Exon 2 of 21	NP_001393670.1	P10253

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAA	ENST00000302262.8	TSL:1 MANE Select	c.-103G>A		5_prime_UTR	Exon 1 of 20	ENSP00000305692.3	P10253
	GAA	ENST00000390015.7	TSL:1	c.-103G>A		5_prime_UTR	Exon 2 of 21	ENSP00000374665.3	P10253
	GAA	ENST00000574376.1	TSL:1	n.39G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 56 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 34

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 42

Other (OTH) AF: 0.00 AC: 0 AN: 8

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.91
DANN	Benign	0.93
PhyloP100		-0.65
PromoterAI		0.0052	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1598564555; hg19: chr17-78075619;