X-121048157-T-C

Variant names:

• chrX-121048157-T-C
• NM_012084.4:c.473T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012084.4(GLUD2):​c.473T>C​(p.Val158Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: GLUD2 NM_012084.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.64
• Publications: 0 publications found

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]

ENSG00000286163 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11889842).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012084.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLUD2	NM_012084.4	MANE Select	c.473T>C	p.Val158Ala	missense	Exon 1 of 1	NP_036216.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLUD2	ENST00000328078.3	TSL:6 MANE Select	c.473T>C	p.Val158Ala	missense	Exon 1 of 1	ENSP00000327589.1	P49448
	ENSG00000286163	ENST00000768679.1		n.61-3080T>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	13
DANN	Benign	0.92
DEOGEN2	Benign	0.13	T
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.12	T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Benign	-0.050	N
PhyloP100		3.6
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.77	N
REVEL	Uncertain	0.37
Sift	Benign	0.71	T
Sift4G	Benign	0.73	T
Polyphen		0.0	B
Vest4		0.19
MutPred		0.52		Loss of stability (P = 0.0129)
MVP		0.89
MPC		0.74
ClinPred		0.62	D
GERP RS		1.6
Varity_R		0.21
gMVP		0.85
Mutation Taster		=52/48	polymorphism

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

Other links and lift over

hg19: chrX-120182011;