rs4825836

Positions:

• chrX-123192466-T-C
• chrX-123192466-T-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000828.5(GRIA3):​c.268+6476T>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 0.72 (20588 hom., 22956 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: GRIA3 NM_000828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.924

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIA3	NM_000828.5	c.268+6476T>C		intron_variant		ENST00000622768.5	NP_000819.4
GRIA3	NM_007325.5	c.268+6476T>C		intron_variant		ENST00000620443.2	NP_015564.5
GRIA3	NM_001256743.2	c.268+6476T>C		intron_variant			NP_001243672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIA3	ENST00000620443.2	c.268+6476T>C		intron_variant		1	NM_007325.5	ENSP00000478489	P4
GRIA3	ENST00000622768.5	c.268+6476T>C		intron_variant		5	NM_000828.5	ENSP00000481554	A1

Frequencies

GnomAD3 genomes AF: 0.722 AC: 79349 AN: 109958 Hom.: 20593 Cov.: 22 AF XY: 0.712 AC XY: 22902 AN XY: 32186

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.868

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.784

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.843

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.715

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: 0.722 AC: 79389 AN: 110012 Hom.: 20588 Cov.: 22 AF XY: 0.712 AC XY: 22956 AN XY: 32250

Gnomad4 AFR AF: 0.689

Gnomad4 AMR AF: 0.692

Gnomad4 ASJ AF: 0.779

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.781

Gnomad4 FIN AF: 0.663

Gnomad4 NFE AF: 0.757

Gnomad4 OTH AF: 0.716

Alfa AF: 0.749 Hom.: 89631

Bravo AF: 0.720

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.91
DANN	Benign	0.39

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: rs4825836; hg19: chrX-122326318;