rs3827431

Positions:

• chrX-123355313-A-G

Variant summary

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

The NM_007325.5(GRIA3):​c.750+350A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 111,777 control chromosomes in the GnomAD database, including 869 homozygotes. There are 4,848 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 0.15 (869 hom., 4848 hem., cov: 23)
• Consequence: GRIA3 NM_007325.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.572

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]

GRIA3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIA3	NM_000828.5	c.750+350A>G		intron_variant		ENST00000622768.5	NP_000819.4
GRIA3	NM_007325.5	c.750+350A>G		intron_variant		ENST00000620443.2	NP_015564.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIA3	ENST00000620443.2	c.750+350A>G		intron_variant		1	NM_007325.5	ENSP00000478489.1
GRIA3	ENST00000622768.5	c.750+350A>G		intron_variant		5	NM_000828.5	ENSP00000481554.1
GRIA3	ENST00000620581.4	n.750+350A>G		intron_variant		1		ENSP00000481875.1
GRIA3	ENST00000477389.1	n.55+350A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.147 AC: 16377 AN: 111722 Hom.: 869 Cov.: 23 AF XY: 0.143 AC XY: 4839 AN XY: 33922

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.0885

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.147 AC: 16382 AN: 111777 Hom.: 869 Cov.: 23 AF XY: 0.143 AC XY: 4848 AN XY: 33987

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.0887

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.148

Alfa AF: 0.131 Hom.: 5626

Bravo AF: 0.152

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.011
DANN	Benign	0.59

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: rs3827431; hg19: chrX-122489164;