Genetic Variant GRIA3:c.508+8793C>G (chrX-123262335-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_007325.5(GRIA3):c.508+8793C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000181 in 110,379 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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 0.000018 ( 0 hom., 1 hem., cov: 23)

Consequence

GRIA3
NM_007325.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.299

Publications

1 publications found

Variant links:

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, Labcorp Genetics (formerly Invitae), G2P
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

GRIA3 links:

ENSG00000307341 (HGNC:):

ENSG00000307341 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA3	NM_000828.5 link	c.508+8793C>G		intron_variant	Intron 3 of 15	ENST00000622768.5	NP_000819.4	P42263-1Q17R51
GRIA3	NM_007325.5 link	c.508+8793C>G		intron_variant	Intron 3 of 15	ENST00000620443.2	NP_015564.5	P42263-2Q17R51

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GRIA3	ENST00000620443.2 link	c.508+8793C>G	intron_variant	Intron 3 of 15	1	NM_007325.5	ENSP00000478489.1	P42263-2
GRIA3	ENST00000622768.5 link	c.508+8793C>G	intron_variant	Intron 3 of 15	5	NM_000828.5	ENSP00000481554.1	P42263-1
GRIA3	ENST00000620581.4 link	n.508+8793C>G	intron_variant	Intron 3 of 16	1		ENSP00000481875.1	A0A087WYJ6
ENSG00000307341	ENST00000825206.1 link	n.667+51510G>C	intron_variant	Intron 6 of 6

Frequencies

GnomAD3 genomes

AF:

0.0000181

AC:

AN:

110379

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000191

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

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

GnomAD4 genome

AF:

0.0000181

AC:

AN:

110379

Hom.:

Cov.:

AF XY:

0.0000306

AC XY:

AN XY:

32671

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30312

American (AMR)

AF:

0.000191

AC:

AN:

10452

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2626

East Asian (EAS)

AF:

0.00

AC:

AN:

3466

South Asian (SAS)

AF:

0.00

AC:

AN:

2541

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5843

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52744

Other (OTH)

AF:

0.00

AC:

AN:

1484

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

2087

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.7

(source)

DANN

Benign

0.74

PhyloP100

0.30

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over