chr4-22747998-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000508166.5(GBA3):c.989C>A(p.Ala330Glu) variant causes a missense 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. 8/9 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
GBA3
ENST00000508166.5 missense
ENST00000508166.5 missense
Scores
7
Clinical Significance
Conservation
PhyloP100: -1.22
Genes affected
GBA3 (HGNC:19069): (glucosylceramidase beta 3 (gene/pseudogene)) The protein encoded by this gene is a cytosolic enzyme that can hydrolyze several types of glycosides. The enzyme has its highest activity at neutral pH and is predominantly expressed in human liver, kidney, intestine, and spleen. This gene is a polymorphic pseudogene, with the most common allele being the functional allele that encodes the full-length protein. Some individuals contain a single nucleotide polymorphism that results in a premature stop codon in the coding region, and therefore this allele is pseudogenic due to the failure to produce a functional full-length protein. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.2023857).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GBA3 | NR_102355.2 | n.1068C>A | non_coding_transcript_exon_variant | 3/5 | |||
GBA3 | NR_102357.2 | n.990C>A | non_coding_transcript_exon_variant | 3/5 | |||
GBA3 | NR_102356.2 | n.365+11790C>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GBA3 | ENST00000508166.5 | c.989C>A | p.Ala330Glu | missense_variant | 3/5 | 1 | P5 | ||
GBA3 | ENST00000503442.1 | c.286+11790C>A | intron_variant | 1 | A2 | ||||
GBA3 | ENST00000511446.2 | c.476C>A | p.Ala159Glu | missense_variant | 3/5 | 2 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1458406Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 725142
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1458406
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
725142
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 17, 2022 | The c.989C>A (p.A330E) alteration is located in exon 3 (coding exon 3) of the GBA3 gene. This alteration results from a C to A substitution at nucleotide position 989, causing the alanine (A) at amino acid position 330 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
PrimateAI
Benign
T
Vest4
MVP
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at