3-30839103-G-A
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_207359.3(GADL1):c.797C>T(p.Pro266Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000139 in 1,584,282 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 (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
GADL1
NM_207359.3 missense
NM_207359.3 missense
Scores
11
7
1
Clinical Significance
Conservation
PhyloP100: 9.60
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, 0.965
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GADL1 | NM_207359.3 | c.797C>T | p.Pro266Leu | missense_variant | 9/15 | ENST00000282538.10 | |
GADL1 | XM_017006297.2 | c.740C>T | p.Pro247Leu | missense_variant | 9/15 | ||
GADL1 | XM_047448071.1 | c.797C>T | p.Pro266Leu | missense_variant | 9/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GADL1 | ENST00000282538.10 | c.797C>T | p.Pro266Leu | missense_variant | 9/15 | 5 | NM_207359.3 | P1 | |
GADL1 | ENST00000454381.3 | c.797C>T | p.Pro266Leu | missense_variant | 9/12 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 151970Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000174 AC: 4AN: 229662Hom.: 0 AF XY: 0.0000241 AC XY: 3AN XY: 124348
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GnomAD4 exome AF: 0.0000126 AC: 18AN: 1432312Hom.: 0 Cov.: 29 AF XY: 0.0000169 AC XY: 12AN XY: 709856
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 151970Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2AN XY: 74202
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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 | Aug 04, 2023 | The c.797C>T (p.P266L) alteration is located in exon 9 (coding exon 9) of the GADL1 gene. This alteration results from a C to T substitution at nucleotide position 797, causing the proline (P) at amino acid position 266 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
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
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