Variant chrX-123202596-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007325.5(GRIA3):c.268+16606T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 1,151,262 control chromosomes in the GnomAD database, including 54,013 homozygotes. There are 134,888 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 ( 5848 hom., 12330 hem., cov: 23)

Exomes 𝑓: 0.37 ( 48165 hom. 122558 hem. )

Consequence

GRIA3
NM_007325.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.08

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
GRIA3	NM_000828.5 link	c.268+16606T>C	intron_variant	ENST00000622768.5	NP_000819.4	P42263-1Q17R51
GRIA3	NM_007325.5 link	c.268+16606T>C	intron_variant	ENST00000620443.2	NP_015564.5	P42263-2Q17R51
GRIA3	NM_001256743.2 link	c.269-40T>C	intron_variant		NP_001243672.1	Q5XKG2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIA3	ENST00000620443.2 link	c.268+16606T>C		intron_variant		1	NM_007325.5	ENSP00000478489.1		P42263-2
GRIA3	ENST00000622768.5 link	c.268+16606T>C		intron_variant		5	NM_000828.5	ENSP00000481554.1		P42263-1

Frequencies

GnomAD3 genomes

AF:

0.382

AC:

42346

AN:

110911

Hom.:

5848

Cov.:

AF XY:

0.371

AC XY:

12297

AN XY:

33163

show subpopulations

Gnomad AFR

AF:

0.406

Gnomad AMI

AF:

0.546

Gnomad AMR

AF:

0.452

Gnomad ASJ

AF:

0.411

Gnomad EAS

AF:

0.477

Gnomad SAS

AF:

0.391

Gnomad FIN

AF:

0.272

Gnomad MID

AF:

0.466

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.388

GnomAD3 exomes

AF:

0.405

AC:

41117

AN:

101601

Hom.:

5941

AF XY:

0.394

AC XY:

13150

AN XY:

33397

show subpopulations

Gnomad AFR exome

AF:

0.417

Gnomad AMR exome

AF:

0.535

Gnomad ASJ exome

AF:

0.401

Gnomad EAS exome

AF:

0.486

Gnomad SAS exome

AF:

0.404

Gnomad FIN exome

AF:

0.290

Gnomad NFE exome

AF:

0.360

Gnomad OTH exome

AF:

0.401

GnomAD4 exome

AF:

0.366

AC:

381207

AN:

1040301

Hom.:

48165

Cov.:

AF XY:

0.367

AC XY:

122558

AN XY:

334079

show subpopulations

Gnomad4 AFR exome

AF:

0.410

Gnomad4 AMR exome

AF:

0.523

Gnomad4 ASJ exome

AF:

0.409

Gnomad4 EAS exome

AF:

0.485

Gnomad4 SAS exome

AF:

0.405

Gnomad4 FIN exome

AF:

0.292

Gnomad4 NFE exome

AF:

0.355

Gnomad4 OTH exome

AF:

0.378

GnomAD4 genome

AF:

0.382

AC:

42366

AN:

110961

Hom.:

5848

Cov.:

AF XY:

0.371

AC XY:

12330

AN XY:

33223

show subpopulations

Gnomad4 AFR

AF:

0.406

Gnomad4 AMR

AF:

0.452

Gnomad4 ASJ

AF:

0.411

Gnomad4 EAS

AF:

0.477

Gnomad4 SAS

AF:

0.388

Gnomad4 FIN

AF:

0.272

Gnomad4 NFE

AF:

0.356

Gnomad4 OTH

AF:

0.392

Alfa

AF:

0.309

Hom.:

3944

Bravo

AF:

0.404

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.27

DANN

Benign

0.79

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over