rs12857357

Variant names:

• chrX-123368728-A-G
• rs12857357
• NM_000828.5:c.750+13765A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-123368728-A-G
• chrX-123368728-A-T

Variant summary

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

The NM_000828.5(GRIA3):​c.750+13765A>G 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 0.16 (1180 hom., 4803 hem., cov: 20)
• Consequence: GRIA3 NM_000828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.241
• 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: 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA3	NM_000828.5	c.750+13765A>G		intron_variant	Intron 5 of 15	ENST00000622768.5	NP_000819.4
GRIA3	NM_007325.5	c.750+13765A>G		intron_variant	Intron 5 of 15	ENST00000620443.2	NP_015564.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIA3	ENST00000620443.2	c.750+13765A>G		intron_variant	Intron 5 of 15	1	NM_007325.5	ENSP00000478489.1
GRIA3	ENST00000622768.5	c.750+13765A>G		intron_variant	Intron 5 of 15	5	NM_000828.5	ENSP00000481554.1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 17575 AN: 107308 Hom.: 1183 Cov.: 20

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.0415

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0826

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.164 AC: 17573 AN: 107348 Hom.: 1180 Cov.: 20 AF XY: 0.159 AC XY: 4803 AN XY: 30192

African (AFR) AF: 0.140 AC: 4060 AN: 29078

American (AMR) AF: 0.264 AC: 2603 AN: 9871

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 278 AN: 2609

East Asian (EAS) AF: 0.254 AC: 857 AN: 3373

South Asian (SAS) AF: 0.350 AC: 841 AN: 2402

European-Finnish (FIN) AF: 0.112 AC: 619 AN: 5516

Middle Eastern (MID) AF: 0.0865 AC: 18 AN: 208

European-Non Finnish (NFE) AF: 0.154 AC: 8019 AN: 52172

Other (OTH) AF: 0.173 AC: 250 AN: 1444

Alfa AF: 0.155 Hom.: 4077

Bravo AF: 0.173

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.80
PhyloP100		-0.24
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: rs12857357; hg19: chrX-122502579;