X-121047856-G-T

Position:

• chrX-121047856-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012084.4(GLUD2):​c.172G>T​(p.Ala58Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 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: 0.257

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07521245).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLUD2	NM_012084.4	c.172G>T	p.Ala58Ser	missense_variant	1/1	ENST00000328078.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLUD2	ENST00000328078.3	c.172G>T	p.Ala58Ser	missense_variant	1/1		NM_012084.4	P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 17, 2023

The c.172G>T (p.A58S) 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 172, causing the alanine (A) at amino acid position 58 to be replaced by a serine (S). 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	Benign	0.081
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	9.6
DANN	Benign	0.83
DEOGEN2	Benign	0.093	T
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.32	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	0.93	N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.35	N
REVEL	Benign	0.17
Sift	Benign	0.35	T
Sift4G	Benign	0.54	T
Polyphen		0.0070	B
Vest4		0.062
MutPred		0.23		Gain of phosphorylation at A58 (P = 0.0292);
MVP		0.95
MPC		0.57
ClinPred		0.11	T
GERP RS		0.54
Varity_R		0.058
gMVP		0.56

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-120181710;