rs12559450

Positions:

• chrX-123191991-G-A
• chrX-123191991-G-C

Variant summary

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

The NM_000828.5(GRIA3):​c.268+6001G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 110,357 control chromosomes in the GnomAD database, including 3,132 homozygotes. There are 8,404 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 0.26 (3132 hom., 8404 hem., cov: 22)
• Consequence: GRIA3 NM_000828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.802

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIA3	NM_000828.5	c.268+6001G>A		intron_variant		ENST00000622768.5	NP_000819.4
GRIA3	NM_007325.5	c.268+6001G>A		intron_variant		ENST00000620443.2	NP_015564.5
GRIA3	NM_001256743.2	c.268+6001G>A		intron_variant			NP_001243672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIA3	ENST00000620443.2	c.268+6001G>A		intron_variant		1	NM_007325.5	ENSP00000478489	P4
GRIA3	ENST00000622768.5	c.268+6001G>A		intron_variant		5	NM_000828.5	ENSP00000481554	A1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 29020 AN: 110305 Hom.: 3127 Cov.: 22 AF XY: 0.258 AC XY: 8395 AN XY: 32597

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.295

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.263 AC: 29035 AN: 110357 Hom.: 3132 Cov.: 22 AF XY: 0.257 AC XY: 8404 AN XY: 32659

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.285

Alfa AF: 0.181 Hom.: 1108

Bravo AF: 0.266

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.50

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: rs12559450; hg19: chrX-122325843;