rs6608062

chrX-123234050-G-AchrX-123234050-G-C

Variant summary

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

The NM_000828.5(GRIA3):c.269-19253G>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 (14142 hom., 19254 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: GRIA3 NM_000828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.644

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=-0.89).
• BS2: High Homozygotes in GnomAd at 14139 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIA3	NM_000828.5	c.269-19253G>A		intron_variant		ENST00000622768.5
GRIA3	NM_007325.5	c.269-19253G>A		intron_variant		ENST00000620443.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIA3	ENST00000620443.2	c.269-19253G>A		intron_variant		1	NM_007325.5	P4
GRIA3	ENST00000622768.5	c.269-19253G>A		intron_variant		5	NM_000828.5	A1
GRIA3	ENST00000620581.4	c.269-19253G>A		intron_variant, NMD_transcript_variant		1
GRIA3	ENST00000479118.1	n.245-19253G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.590 AC: 64770 AN: 109691 Hom.: 14139 Cov.: 22 AF XY: 0.600 AC XY: 19229 AN XY: 32069

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.678

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.614

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: 0.590 AC: 64792 AN: 109744 Hom.: 14142 Cov.: 22 AF XY: 0.599 AC XY: 19254 AN XY: 32132

Gnomad4 AFR AF: 0.397

Gnomad4 AMR AF: 0.739

Gnomad4 ASJ AF: 0.653

Gnomad4 EAS AF: 0.977

Gnomad4 SAS AF: 0.808

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.619

Alfa AF: 0.638 Hom.: 42766

Bravo AF: 0.596

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.3
Dann	Benign	0.48

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: rs6608062; hg19: chrX-122367901;