rs4825857

Variant names:

• chrX-123362513-C-A
• rs4825857
• NM_000828.5:c.750+7550C>A

Variant summary

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

The NM_007325.5(GRIA3):​c.750+7550C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 109,812 control chromosomes in the GnomAD database, including 6,144 homozygotes. There are 12,151 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 0.38 (6144 hom., 12151 hem., cov: 22)
• Consequence: GRIA3 NM_007325.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123
• 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.441 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.750+7550C>A		intron	N/A	NP_000819.4	P42263-1
	GRIA3	NM_007325.5	MANE Select	c.750+7550C>A		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.750+7550C>A		intron	N/A	ENSP00000478489.1	P42263-2
	GRIA3	ENST00000622768.5	TSL:5 MANE Plus Clinical	c.750+7550C>A		intron	N/A	ENSP00000481554.1	P42263-1
	GRIA3	ENST00000620581.4	TSL:1	n.750+7550C>A		intron	N/A	ENSP00000481875.1	A0A087WYJ6

Frequencies

GnomAD3 genomes AF: 0.384 AC: 42160 AN: 109761 Hom.: 6142 Cov.: 22

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.384 AC: 42169 AN: 109812 Hom.: 6144 Cov.: 22 AF XY: 0.378 AC XY: 12151 AN XY: 32156

African (AFR) AF: 0.268 AC: 8120 AN: 30245

American (AMR) AF: 0.364 AC: 3751 AN: 10304

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1407 AN: 2619

East Asian (EAS) AF: 0.338 AC: 1170 AN: 3458

South Asian (SAS) AF: 0.331 AC: 840 AN: 2541

European-Finnish (FIN) AF: 0.428 AC: 2437 AN: 5695

Middle Eastern (MID) AF: 0.552 AC: 117 AN: 212

European-Non Finnish (NFE) AF: 0.446 AC: 23420 AN: 52567

Other (OTH) AF: 0.396 AC: 595 AN: 1504

Alfa AF: 0.427 Hom.: 53833

Bravo AF: 0.381

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.6
DANN	Benign	0.80
PhyloP100		0.12
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: rs4825857; hg19: chrX-122496364;