chrX-123263410-G-A

Variant names:

• chrX-123263410-G-A
• rs695214
• NM_000828.5:c.508+9868G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000828.5(GRIA3):​c.508+9868G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0543 in 111,917 control chromosomes in the GnomAD database, including 173 homozygotes. There are 1,851 hemizygotes in GnomAD. 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 0.054 (173 hom., 1851 hem., cov: 24)
• Consequence: GRIA3 NM_000828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920
• Publications: 2 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0741 is higher than 0.05.

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.508+9868G>A		intron	N/A	NP_000819.4
	GRIA3	NM_007325.5	MANE Select	c.508+9868G>A		intron	N/A	NP_015564.5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA3	ENST00000620443.2	TSL:1 MANE Select	c.508+9868G>A		intron	N/A	ENSP00000478489.1
	GRIA3	ENST00000622768.5	TSL:5 MANE Plus Clinical	c.508+9868G>A		intron	N/A	ENSP00000481554.1
	GRIA3	ENST00000620581.4	TSL:1	n.508+9868G>A		intron	N/A	ENSP00000481875.1

Frequencies

GnomAD3 genomes AF: 0.0544 AC: 6086 AN: 111866 Hom.: 173 Cov.: 24

Gnomad AFR AF: 0.00937

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.0359

Gnomad ASJ AF: 0.0855

Gnomad EAS AF: 0.000281

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0667

Gnomad NFE AF: 0.0760

Gnomad OTH AF: 0.0518

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

GnomAD4 genome AF: 0.0543 AC: 6081 AN: 111917 Hom.: 173 Cov.: 24 AF XY: 0.0542 AC XY: 1851 AN XY: 34153

African (AFR) AF: 0.00932 AC: 288 AN: 30904

American (AMR) AF: 0.0359 AC: 382 AN: 10644

Ashkenazi Jewish (ASJ) AF: 0.0855 AC: 226 AN: 2643

East Asian (EAS) AF: 0.000282 AC: 1 AN: 3544

South Asian (SAS) AF: 0.0120 AC: 32 AN: 2656

European-Finnish (FIN) AF: 0.144 AC: 870 AN: 6040

Middle Eastern (MID) AF: 0.0639 AC: 14 AN: 219

European-Non Finnish (NFE) AF: 0.0760 AC: 4035 AN: 53064

Other (OTH) AF: 0.0512 AC: 78 AN: 1524

Alfa AF: 0.0668 Hom.: 4926

Bravo AF: 0.0457

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	9.8
DANN	Benign	0.82
PhyloP100		0.092
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: rs695214; hg19: chrX-122397261;