rs5910001

chrX-123375442-C-T

Variant summary

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

The NM_000828.5(GRIA3):c.751-19526C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 110,783 control chromosomes in the GnomAD database, including 1,086 homozygotes. There are 4,741 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 (1086 hom., 4741 hem., cov: 23)
• Consequence: GRIA3 NM_000828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.921

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=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIA3	NM_000828.5	c.751-19526C>T		intron_variant		ENST00000622768.5
GRIA3	NM_007325.5	c.751-19526C>T		intron_variant		ENST00000620443.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIA3	ENST00000620443.2	c.751-19526C>T		intron_variant		1	NM_007325.5	P4
GRIA3	ENST00000622768.5	c.751-19526C>T		intron_variant		5	NM_000828.5	A1
GRIA3	ENST00000620581.4	c.751-19526C>T		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 16757 AN: 110731 Hom.: 1087 Cov.: 23 AF XY: 0.143 AC XY: 4736 AN XY: 33067

Gnomad AFR AF: 0.0897

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.0218

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.151 AC: 16756 AN: 110783 Hom.: 1086 Cov.: 23 AF XY: 0.143 AC XY: 4741 AN XY: 33129

Gnomad4 AFR AF: 0.0896

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.0219

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.138

Alfa AF: 0.182 Hom.: 3593

Bravo AF: 0.141

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.68
Dann	Benign	0.23

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: rs5910001; hg19: chrX-122509293;