rs687577

chrX-123445253-A-CchrX-123445253-A-T

Variant summary

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

The NM_000828.5(GRIA3):c.2076+17114A>C 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 0.82 (26376 hom., 26718 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: GRIA3 NM_000828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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=-0.94).
• BS2: High Homozygotes in GnomAd at 26383 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIA3	NM_000828.5	c.2076+17114A>C		intron_variant		ENST00000622768.5
GRIA3	NM_007325.5	c.2076+17114A>C		intron_variant		ENST00000620443.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIA3	ENST00000620443.2	c.2076+17114A>C		intron_variant		1	NM_007325.5	P4
GRIA3	ENST00000622768.5	c.2076+17114A>C		intron_variant		5	NM_000828.5	A1
GRIA3	ENST00000620581.4	c.2076+17114A>C		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.819 AC: 90394 AN: 110418 Hom.: 26383 Cov.: 23 AF XY: 0.817 AC XY: 26676 AN XY: 32650

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.933

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.878

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.884

Gnomad OTH AF: 0.815

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: 0.819 AC: 90425 AN: 110471 Hom.: 26376 Cov.: 23 AF XY: 0.817 AC XY: 26718 AN XY: 32713

Gnomad4 AFR AF: 0.703

Gnomad4 AMR AF: 0.836

Gnomad4 ASJ AF: 0.856

Gnomad4 EAS AF: 0.701

Gnomad4 SAS AF: 0.730

Gnomad4 FIN AF: 0.878

Gnomad4 NFE AF: 0.884

Gnomad4 OTH AF: 0.809

Alfa AF: 0.864 Hom.: 66032

Bravo AF: 0.815

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.082
Dann	Benign	0.33

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: rs687577; hg19: chrX-122579104;