rs695214

Positions:

• chrX-123263410-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_007325.5(GRIA3):​c.508+9868G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0543 in 111,917 control chromosomes in the GnomAD database, including 173 homozygotes. There are 1,851 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 0.054 (173 hom., 1851 hem., cov: 24)
• Consequence: GRIA3 NM_007325.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIA3	NM_000828.5	c.508+9868G>A		intron_variant		ENST00000622768.5	NP_000819.4
GRIA3	NM_007325.5	c.508+9868G>A		intron_variant		ENST00000620443.2	NP_015564.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIA3	ENST00000620443.2	c.508+9868G>A		intron_variant		1	NM_007325.5	ENSP00000478489.1
GRIA3	ENST00000622768.5	c.508+9868G>A		intron_variant		5	NM_000828.5	ENSP00000481554.1
GRIA3	ENST00000620581.4	n.508+9868G>A		intron_variant		1		ENSP00000481875.1

Frequencies

GnomAD3 genomes AF: 0.0544 AC: 6086 AN: 111866 Hom.: 173 Cov.: 24 AF XY: 0.0544 AC XY: 1855 AN XY: 34092

Gnomad AFR AF: 0.00937

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.0359

Gnomad ASJ AF: 0.0855

Gnomad EAS AF: 0.000281

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0667

Gnomad NFE AF: 0.0760

Gnomad OTH AF: 0.0518

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

GnomAD4 genome AF: 0.0543 AC: 6081 AN: 111917 Hom.: 173 Cov.: 24 AF XY: 0.0542 AC XY: 1851 AN XY: 34153

Gnomad4 AFR AF: 0.00932

Gnomad4 AMR AF: 0.0359

Gnomad4 ASJ AF: 0.0855

Gnomad4 EAS AF: 0.000282

Gnomad4 SAS AF: 0.0120

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.0760

Gnomad4 OTH AF: 0.0512

Alfa AF: 0.0708 Hom.: 3460

Bravo AF: 0.0457

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	9.8
DANN	Benign	0.82

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: rs695214; hg19: chrX-122397261;