rs2187797

Variant names:

• chrX-123193389-A-C
• rs2187797
• NM_000828.5:c.268+7399A>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000828.5(GRIA3):​c.268+7399A>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 (20289 hom., 22973 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: GRIA3 NM_000828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.370
• Publications: 1 publications found

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]

GRIA3 Gene-Disease associations (from GenCC):

• syndromic X-linked intellectual disability 94

  Inheritance: XL Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• X-linked complex neurodevelopmental disorder

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• X-linked intellectual disability due to GRIA3 anomalies

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000307341 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000828.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA3	NM_000828.5	MANE Plus Clinical	c.268+7399A>C		intron	N/A	NP_000819.4
	GRIA3	NM_007325.5	MANE Select	c.268+7399A>C		intron	N/A	NP_015564.5
	GRIA3	NM_001256743.2		c.268+7399A>C		intron	N/A	NP_001243672.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA3	ENST00000620443.2	TSL:1 MANE Select	c.268+7399A>C		intron	N/A	ENSP00000478489.1
	GRIA3	ENST00000622768.5	TSL:5 MANE Plus Clinical	c.268+7399A>C		intron	N/A	ENSP00000481554.1
	GRIA3	ENST00000611689.4	TSL:1	c.268+7399A>C		intron	N/A	ENSP00000478758.1

Frequencies

GnomAD3 genomes AF: 0.717 AC: 78984 AN: 110219 Hom.: 20294 Cov.: 23

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.777

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.784

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.843

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.712

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: 0.717 AC: 79021 AN: 110270 Hom.: 20289 Cov.: 23 AF XY: 0.706 AC XY: 22973 AN XY: 32546

African (AFR) AF: 0.688 AC: 20833 AN: 30266

American (AMR) AF: 0.688 AC: 7135 AN: 10368

Ashkenazi Jewish (ASJ) AF: 0.777 AC: 2039 AN: 2625

East Asian (EAS) AF: 0.533 AC: 1848 AN: 3468

South Asian (SAS) AF: 0.781 AC: 1988 AN: 2545

European-Finnish (FIN) AF: 0.665 AC: 3901 AN: 5867

Middle Eastern (MID) AF: 0.836 AC: 179 AN: 214

European-Non Finnish (NFE) AF: 0.748 AC: 39435 AN: 52731

Other (OTH) AF: 0.713 AC: 1076 AN: 1509

Alfa AF: 0.717 Hom.: 14129

Bravo AF: 0.715

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Benign	0.81
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2187797; hg19: chrX-122327241;