X-121048135-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong

The NM_012084.4(GLUD2):​c.451C>T​(p.Arg151Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., 0 hem., cov: 23)
Exomes 𝑓: 0.0000027 ( 0 hom. 2 hem. )
Failed GnomAD Quality Control

Consequence

GLUD2
NM_012084.4 missense

Scores

9
5
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.74
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.959

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GLUD2NM_012084.4 linkc.451C>T p.Arg151Cys missense_variant Exon 1 of 1 ENST00000328078.3 NP_036216.2 P49448A0A140VK14

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GLUD2ENST00000328078.3 linkc.451C>T p.Arg151Cys missense_variant Exon 1 of 1 6 NM_012084.4 ENSP00000327589.1 P49448

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
112246
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34404
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000273
AC:
3
AN:
1098084
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
2
AN XY:
363460
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000237
Gnomad4 OTH exome
AF:
0.0000217
GnomAD4 genome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
112246
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34404
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 16, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.451C>T (p.R151C) alteration is located in exon 1 (coding exon 1) of the GLUD2 gene. This alteration results from a C to T substitution at nucleotide position 451, causing the arginine (R) at amino acid position 151 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.93
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.16
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.75
D
FATHMM_MKL
Benign
0.62
D
LIST_S2
Uncertain
0.95
D
M_CAP
Uncertain
0.19
D
MetaRNN
Pathogenic
0.96
D
MetaSVM
Pathogenic
1.0
D
MutationAssessor
Pathogenic
5.2
H
PrimateAI
Benign
0.37
T
PROVEAN
Pathogenic
-6.7
D
REVEL
Pathogenic
0.68
Sift
Uncertain
0.011
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.38
MutPred
0.95
Loss of MoRF binding (P = 0.0322);
MVP
0.88
MPC
1.9
ClinPred
1.0
D
GERP RS
-0.30
Varity_R
0.60
gMVP
0.99

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-120181989; COSMIC: COSV105244645; API