rs5911592

Variant names:

• chrX-123328711-C-T
• rs5911592
• NM_000828.5:c.696+2498C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007325.5(GRIA3):​c.696+2498C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 110,932 control chromosomes in the GnomAD database, including 1,656 homozygotes. There are 6,009 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 0.19 (1656 hom., 6009 hem., cov: 22)
• Consequence: GRIA3 NM_007325.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.836
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• syndromic X-linked intellectual disability 94

  Inheritance: XL Classification: DEFINITIVE, STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• X-linked complex neurodevelopmental disorder

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• X-linked intellectual disability due to GRIA3 anomalies

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000307341 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007325.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA3	NM_000828.5	MANE Plus Clinical	c.696+2498C>T		intron	N/A	NP_000819.4	P42263-1
	GRIA3	NM_007325.5	MANE Select	c.696+2498C>T		intron	N/A	NP_015564.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA3	ENST00000620443.2	TSL:1 MANE Select	c.696+2498C>T		intron	N/A	ENSP00000478489.1	P42263-2
	GRIA3	ENST00000622768.5	TSL:5 MANE Plus Clinical	c.696+2498C>T		intron	N/A	ENSP00000481554.1	P42263-1
	GRIA3	ENST00000620581.4	TSL:1	n.696+2498C>T		intron	N/A	ENSP00000481875.1	A0A087WYJ6

Frequencies

GnomAD3 genomes AF: 0.194 AC: 21486 AN: 110882 Hom.: 1657 Cov.: 22

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.0115

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.194 AC: 21507 AN: 110932 Hom.: 1656 Cov.: 22 AF XY: 0.181 AC XY: 6009 AN XY: 33226

African (AFR) AF: 0.203 AC: 6204 AN: 30547

American (AMR) AF: 0.123 AC: 1293 AN: 10503

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 461 AN: 2637

East Asian (EAS) AF: 0.0115 AC: 41 AN: 3558

South Asian (SAS) AF: 0.109 AC: 287 AN: 2636

European-Finnish (FIN) AF: 0.197 AC: 1165 AN: 5900

Middle Eastern (MID) AF: 0.142 AC: 30 AN: 212

European-Non Finnish (NFE) AF: 0.221 AC: 11662 AN: 52753

Other (OTH) AF: 0.170 AC: 256 AN: 1509

Alfa AF: 0.206 Hom.: 6238

Bravo AF: 0.188

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.6
DANN	Benign	0.78
PhyloP100		-0.84
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5911592; hg19: chrX-122462562;