rs988146631

Positions:

• chrX-123428043-G-A
• chrX-123428043-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007325.5(GRIA3):​c.1980G>A​(p.Arg660Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.000000926 in 1,080,231 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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: not found (cov: 22)
  • Exomes 𝑓: 9.3e-7 (0 hom. 0 hem.)
• Consequence: GRIA3 NM_007325.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.27

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIA3	NM_000828.5	c.1980G>A	p.Arg660Arg	synonymous_variant	12/16	ENST00000622768.5	NP_000819.4
GRIA3	NM_007325.5	c.1980G>A	p.Arg660Arg	synonymous_variant	12/16	ENST00000620443.2	NP_015564.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIA3	ENST00000620443.2	c.1980G>A	p.Arg660Arg	synonymous_variant	12/16	1	NM_007325.5	ENSP00000478489.1
GRIA3	ENST00000622768.5	c.1980G>A	p.Arg660Arg	synonymous_variant	12/16	5	NM_000828.5	ENSP00000481554.1
GRIA3	ENST00000620581.4	n.1980G>A		non_coding_transcript_exon_variant	12/17	1		ENSP00000481875.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.26e-7 AC: 1 AN: 1080231 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 347239

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000284

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	7.5
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs988146631; hg19: chrX-122561894;