rs765561257
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM5
The NM_001080.3(ALDH5A1):c.278G>A(p.Cys93Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C93F) has been classified as Pathogenic.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
ALDH5A1
NM_001080.3 missense
NM_001080.3 missense
Scores
3
10
6
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 3.17
Genes affected
ALDH5A1 (HGNC:408): (aldehyde dehydrogenase 5 family member A1) This protein belongs to the aldehyde dehydrogenase family of proteins. This gene encodes a mitochondrial NAD(+)-dependent succinic semialdehyde dehydrogenase. A deficiency of this enzyme, known as 4-hydroxybutyricaciduria, is a rare inborn error in the metabolism of the neurotransmitter 4-aminobutyric acid (GABA). In response to the defect, physiologic fluids from patients accumulate GHB, a compound with numerous neuromodulatory properties. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM5
?
Other missense variant is known to change same aminoacid residue: Variant chr6-24495274-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 449408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALDH5A1 | NM_001080.3 | c.278G>A | p.Cys93Tyr | missense_variant | 1/10 | ENST00000357578.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALDH5A1 | ENST00000357578.8 | c.278G>A | p.Cys93Tyr | missense_variant | 1/10 | 1 | NM_001080.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1380650Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 681260
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1380650
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
681260
Gnomad4 AFR exome
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Gnomad4 EAS exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 OTH exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Benign
DEOGEN2
Uncertain
T;T;.
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
D;T;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
N;N;N
REVEL
Uncertain
Sift
Uncertain
D;T;D
Sift4G
Benign
T;T;T
Polyphen
D;.;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0714);Gain of MoRF binding (P = 0.0714);Gain of MoRF binding (P = 0.0714);
MVP
MPC
0.53
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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