chrX-121048057-G-T
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Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting
The NM_012084.4(GLUD2):c.373G>T(p.Asp125Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,210,108 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000036 ( 0 hom., 2 hem., cov: 23)
Exomes 𝑓: 0.000010 ( 0 hom. 5 hem. )
Consequence
GLUD2
NM_012084.4 missense
NM_012084.4 missense
Scores
5
8
4
Clinical Significance
Conservation
PhyloP100: 5.03
Genes affected
GLUD2 (HGNC:4336): (glutamate dehydrogenase 2) The protein encoded by this gene is localized to the mitochondrion and acts as a homohexamer to recycle glutamate during neurotransmission. The encoded enzyme catalyzes the reversible oxidative deamination of glutamate to alpha-ketoglutarate. This gene is intronless.[provided by RefSeq, Jan 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
BS2
High Hemizygotes in GnomAd4 at 2 geneVariant has number of hemizygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLUD2 | NM_012084.4 | c.373G>T | p.Asp125Tyr | missense_variant | 1/1 | ENST00000328078.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLUD2 | ENST00000328078.3 | c.373G>T | p.Asp125Tyr | missense_variant | 1/1 | NM_012084.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000357 AC: 4AN: 112050Hom.: 0 Cov.: 23 AF XY: 0.0000585 AC XY: 2AN XY: 34214
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GnomAD3 exomes AF: 0.0000819 AC: 15AN: 183146Hom.: 0 AF XY: 0.0000886 AC XY: 6AN XY: 67684
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GnomAD4 exome AF: 0.0000100 AC: 11AN: 1098058Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 5AN XY: 363432
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GnomAD4 genome AF: 0.0000357 AC: 4AN: 112050Hom.: 0 Cov.: 23 AF XY: 0.0000585 AC XY: 2AN XY: 34214
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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 | Dec 22, 2023 | The c.373G>T (p.D125Y) alteration is located in exon 1 (coding exon 1) of the GLUD2 gene. This alteration results from a G to T substitution at nucleotide position 373, causing the aspartic acid (D) at amino acid position 125 to be replaced by a tyrosine (Y). 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
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Benign
DEOGEN2
Uncertain
D
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of MoRF binding (P = 0.0563);
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