rs612595

chrX-123402275-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000828.5(GRIA3):c.1081-719C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.59 (13651 hom., 18864 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: GRIA3 NM_000828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS2: High Homozygotes in GnomAd at 13652 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIA3	NM_000828.5	c.1081-719C>A		intron_variant		ENST00000622768.5
GRIA3	NM_007325.5	c.1081-719C>A		intron_variant		ENST00000620443.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIA3	ENST00000620443.2	c.1081-719C>A		intron_variant		1	NM_007325.5	P4
GRIA3	ENST00000622768.5	c.1081-719C>A		intron_variant		5	NM_000828.5	A1
GRIA3	ENST00000620581.4	c.1081-719C>A		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.594 AC: 64827 AN: 109192 Hom.: 13652 Cov.: 22 AF XY: 0.596 AC XY: 18824 AN XY: 31578

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.648

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.573

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.594 AC: 64865 AN: 109238 Hom.: 13651 Cov.: 22 AF XY: 0.596 AC XY: 18864 AN XY: 31634

Gnomad4 AFR AF: 0.560

Gnomad4 AMR AF: 0.587

Gnomad4 ASJ AF: 0.645

Gnomad4 EAS AF: 0.633

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.723

Gnomad4 NFE AF: 0.601

Gnomad4 OTH AF: 0.579

Alfa AF: 0.595 Hom.: 15928

Bravo AF: 0.589

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.0
Dann	Benign	0.62

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: rs612595; hg19: chrX-122536126;