chr3-30800950-A-C
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_207359.3(GADL1):āc.1189T>Gā(p.Trp397Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 31)
Exomes š: 0.0000096 ( 0 hom. )
Consequence
GADL1
NM_207359.3 missense
NM_207359.3 missense
Scores
13
4
2
Clinical Significance
Conservation
PhyloP100: 8.95
Genes affected
GADL1 (HGNC:27949): (glutamate decarboxylase like 1) Predicted to enable aspartate 1-decarboxylase activity; pyridoxal phosphate binding activity; and sulfinoalanine decarboxylase activity. Predicted to be involved in carboxylic acid metabolic process. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.975
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GADL1 | NM_207359.3 | c.1189T>G | p.Trp397Gly | missense_variant | 12/15 | ENST00000282538.10 | |
GADL1 | XM_017006297.2 | c.1132T>G | p.Trp378Gly | missense_variant | 12/15 | ||
GADL1 | XM_047448071.1 | c.1189T>G | p.Trp397Gly | missense_variant | 12/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GADL1 | ENST00000282538.10 | c.1189T>G | p.Trp397Gly | missense_variant | 12/15 | 5 | NM_207359.3 | P1 | |
GADL1 | ENST00000454381.3 | c.1189T>G | p.Trp397Gly | missense_variant | 12/12 | 1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
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31
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251310Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135844
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GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461662Hom.: 0 Cov.: 34 AF XY: 0.00000825 AC XY: 6AN XY: 727138
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GnomAD4 genome Cov.: 31
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31
Asia WGS
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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 | Feb 28, 2023 | The c.1189T>G (p.W397G) alteration is located in exon 12 (coding exon 12) of the GADL1 gene. This alteration results from a T to G substitution at nucleotide position 1189, causing the tryptophan (W) at amino acid position 397 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;H
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MutPred
Loss of MoRF binding (P = 0.0334);Loss of MoRF binding (P = 0.0334);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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