rs5911592

Positions:

• chrX-123328711-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000620443.2(GRIA3):​c.696+2498C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 110,932 control chromosomes in the GnomAD database, including 1,656 homozygotes. There are 6,009 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (1656 hom., 6009 hem., cov: 22)
• Consequence: GRIA3 ENST00000620443.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.836

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIA3	NM_000828.5	c.696+2498C>T		intron_variant		ENST00000622768.5	NP_000819.4
GRIA3	NM_007325.5	c.696+2498C>T		intron_variant		ENST00000620443.2	NP_015564.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIA3	ENST00000620443.2	c.696+2498C>T		intron_variant		1	NM_007325.5	ENSP00000478489	P4
GRIA3	ENST00000622768.5	c.696+2498C>T		intron_variant		5	NM_000828.5	ENSP00000481554	A1
GRIA3	ENST00000620581.4	c.696+2498C>T		intron_variant, NMD_transcript_variant		1		ENSP00000481875

Frequencies

GnomAD3 genomes AF: 0.194 AC: 21486 AN: 110882 Hom.: 1657 Cov.: 22 AF XY: 0.181 AC XY: 5987 AN XY: 33166

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.0115

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.172

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.194 AC: 21507 AN: 110932 Hom.: 1656 Cov.: 22 AF XY: 0.181 AC XY: 6009 AN XY: 33226

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.0115

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.170

Alfa AF: 0.209 Hom.: 4315

Bravo AF: 0.188

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.6
DANN	Benign	0.78

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

LitVar

Other links and lift over

dbSNP: rs5911592; hg19: chrX-122462562;