chrX-123436860-G-T

Variant names:

• chrX-123436860-G-T
• rs6649011
• NM_000828.5:c.2076+8721G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007325.5(GRIA3):​c.2076+8721G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0196 in 110,635 control chromosomes in the GnomAD database, including 74 homozygotes. There are 821 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 0.020 (74 hom., 821 hem., cov: 21)
• Consequence: GRIA3 NM_007325.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36
• Publications: 0 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007325.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA3	NM_000828.5	MANE Plus Clinical	c.2076+8721G>T		intron	N/A	NP_000819.4	P42263-1
	GRIA3	NM_007325.5	MANE Select	c.2076+8721G>T		intron	N/A	NP_015564.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA3	ENST00000620443.2	TSL:1 MANE Select	c.2076+8721G>T		intron	N/A	ENSP00000478489.1	P42263-2
	GRIA3	ENST00000622768.5	TSL:5 MANE Plus Clinical	c.2076+8721G>T		intron	N/A	ENSP00000481554.1	P42263-1
	GRIA3	ENST00000620581.4	TSL:1	n.2076+8721G>T		intron	N/A	ENSP00000481875.1	A0A087WYJ6

Frequencies

GnomAD3 genomes AF: 0.0196 AC: 2164 AN: 110583 Hom.: 72 Cov.: 21

Gnomad AFR AF: 0.00325

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0605

Gnomad ASJ AF: 0.00341

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.0399

Gnomad FIN AF: 0.0834

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00336

Gnomad OTH AF: 0.0269

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

GnomAD4 genome AF: 0.0196 AC: 2170 AN: 110635 Hom.: 74 Cov.: 21 AF XY: 0.0249 AC XY: 821 AN XY: 32911

African (AFR) AF: 0.00325 AC: 99 AN: 30493

American (AMR) AF: 0.0611 AC: 629 AN: 10300

Ashkenazi Jewish (ASJ) AF: 0.00341 AC: 9 AN: 2636

East Asian (EAS) AF: 0.180 AC: 625 AN: 3477

South Asian (SAS) AF: 0.0393 AC: 102 AN: 2596

European-Finnish (FIN) AF: 0.0834 AC: 485 AN: 5814

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.00336 AC: 178 AN: 52912

Other (OTH) AF: 0.0286 AC: 43 AN: 1506

Alfa AF: 0.0127 Hom.: 789

Bravo AF: 0.0226

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	11
DANN	Benign	0.64
PhyloP100		1.4
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: rs6649011; hg19: chrX-122570711;