chrX-121048096-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 6P and 1B. PVS1_StrongPP5_ModerateBS2_Supporting
The NM_012084.4(GLUD2):c.412C>T(p.Gln138Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.000288 in 1,210,112 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 96 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: 𝑓 0.00019 ( 0 hom., 6 hem., cov: 23)
Exomes 𝑓: 0.00030 ( 0 hom. 90 hem. )
Consequence
GLUD2
NM_012084.4 stop_gained
NM_012084.4 stop_gained
Scores
2
1
2
Clinical Significance
Conservation
PhyloP100: 5.34
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 Uncertain_significance. Variant got 5 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.754 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
PP5
Variant X-121048096-C-T is Pathogenic according to our data. Variant chrX-121048096-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2690949.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Hemizygotes in GnomAd4 at 6 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.412C>T | p.Gln138Ter | stop_gained | 1/1 | ENST00000328078.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLUD2 | ENST00000328078.3 | c.412C>T | p.Gln138Ter | stop_gained | 1/1 | NM_012084.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000187 AC: 21AN: 112060Hom.: 0 Cov.: 23 AF XY: 0.000175 AC XY: 6AN XY: 34228
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GnomAD3 exomes AF: 0.000256 AC: 47AN: 183312Hom.: 0 AF XY: 0.000192 AC XY: 13AN XY: 67798
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GnomAD4 exome AF: 0.000298 AC: 327AN: 1098052Hom.: 0 Cov.: 31 AF XY: 0.000248 AC XY: 90AN XY: 363450
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GnomAD4 genome AF: 0.000187 AC: 21AN: 112060Hom.: 0 Cov.: 23 AF XY: 0.000175 AC XY: 6AN XY: 34228
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Male infertility with azoospermia or oligozoospermia due to single gene mutation Pathogenic:1
Likely pathogenic, criteria provided, single submitter | research | Laan Lab, Human Genetics Research Group, University of Tartu | Sep 01, 2023 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
FATHMM_MKL
Benign
D
MutationTaster
Benign
D
Vest4
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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