X-123184576-C-T

Position:

• chrX-123184576-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_007325.5(GRIA3):​c.41C>T​(p.Ala14Val) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 20)
• Consequence: GRIA3 NM_007325.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.83

Genes affected

GRIA3 (HGNC:4573): (glutamate ionotropic receptor AMPA type subunit 3) Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. These receptors are heteromeric protein complexes composed of multiple subunits, arranged to form ligand-gated ion channels. The classification of glutamate receptors is based on their activation by different pharmacologic agonists. The subunit encoded by this gene belongs to a family of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate)-sensitive glutamate receptors, and is subject to RNA editing (AGA->GGA; R->G). Alternative splicing at this locus results in different isoforms, which may vary in their signal transduction properties. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31650776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIA3	NM_000828.5	c.41C>T	p.Ala14Val	missense_variant	1/16	ENST00000622768.5	NP_000819.4
GRIA3	NM_007325.5	c.41C>T	p.Ala14Val	missense_variant	1/16	ENST00000620443.2	NP_015564.5
GRIA3	NM_001256743.2	c.41C>T	p.Ala14Val	missense_variant	1/4		NP_001243672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIA3	ENST00000620443.2	c.41C>T	p.Ala14Val	missense_variant	1/16	1	NM_007325.5	ENSP00000478489.1
GRIA3	ENST00000622768.5	c.41C>T	p.Ala14Val	missense_variant	1/16	5	NM_000828.5	ENSP00000481554.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.052	T;T;T;T;T;.
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	.;D;D;D;.;D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.32	T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	.;N;.;.;N;N
PrimateAI	Uncertain	0.49	T
Sift4G	Benign	0.082	T;T;T;T;T;T
Polyphen		0.033, 0.056	.;B;.;.;B;B
Vest4		0.47
MutPred		0.44		Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);
MVP		0.79
ClinPred		0.65	D
GERP RS		5.3
Varity_R		0.14
gMVP		0.70

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-122318428; COSMIC: COSV52053396;