X-123481804-T-C

Position:

• chrX-123481804-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000828.5(GRIA3):​c.2440-995T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 111,107 control chromosomes in the GnomAD database, including 5,570 homozygotes. There are 12,092 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 0.36 (5570 hom., 12092 hem., cov: 23)
• Consequence: GRIA3 NM_000828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIA3	NM_000828.5	c.2440-995T>C		intron_variant		ENST00000622768.5
GRIA3	NM_007325.5	c.2440-995T>C		intron_variant		ENST00000620443.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIA3	ENST00000620443.2	c.2440-995T>C		intron_variant		1	NM_007325.5	P4
GRIA3	ENST00000622768.5	c.2440-995T>C		intron_variant		5	NM_000828.5	A1
GRIA3	ENST00000620581.4	c.*80-995T>C		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 40041 AN: 111056 Hom.: 5577 Cov.: 23 AF XY: 0.363 AC XY: 12082 AN XY: 33252

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.360 AC: 40025 AN: 111107 Hom.: 5570 Cov.: 23 AF XY: 0.363 AC XY: 12092 AN XY: 33313

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.358

Alfa AF: 0.433 Hom.: 37641

Bravo AF: 0.350

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	12
DANN	Benign	0.76

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

Other links and lift over

dbSNP: rs5910006; hg19: chrX-122615655;