rs2354037

Variant names:

• chrX-123447351-T-C
• rs2354037
• NM_000828.5:c.2077-17514T>C

Your query was ambiguous. Multiple possible variants found:

• chrX-123447351-T-C
• chrX-123447351-T-G

Variant summary

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

The NM_000828.5(GRIA3):​c.2077-17514T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 111,248 control chromosomes in the GnomAD database, including 2,842 homozygotes. There are 8,024 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 0.24 (2842 hom., 8024 hem., cov: 23)
• Consequence: GRIA3 NM_000828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.33 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.2077-17514T>C		intron	N/A	NP_000819.4
	GRIA3	NM_007325.5	MANE Select	c.2077-17514T>C		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.2077-17514T>C		intron	N/A	ENSP00000478489.1
	GRIA3	ENST00000622768.5	TSL:5 MANE Plus Clinical	c.2077-17514T>C		intron	N/A	ENSP00000481554.1
	GRIA3	ENST00000620581.4	TSL:1	n.2077-17514T>C		intron	N/A	ENSP00000481875.1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 26845 AN: 111194 Hom.: 2840 Cov.: 23

Gnomad AFR AF: 0.0536

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.251

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.241 AC: 26845 AN: 111248 Hom.: 2842 Cov.: 23 AF XY: 0.239 AC XY: 8024 AN XY: 33512

African (AFR) AF: 0.0535 AC: 1652 AN: 30878

American (AMR) AF: 0.292 AC: 3075 AN: 10514

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 682 AN: 2642

East Asian (EAS) AF: 0.346 AC: 1209 AN: 3492

South Asian (SAS) AF: 0.318 AC: 847 AN: 2660

European-Finnish (FIN) AF: 0.328 AC: 1915 AN: 5841

Middle Eastern (MID) AF: 0.248 AC: 54 AN: 218

European-Non Finnish (NFE) AF: 0.319 AC: 16826 AN: 52805

Other (OTH) AF: 0.252 AC: 384 AN: 1526

Alfa AF: 0.267 Hom.: 18248

Bravo AF: 0.235

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.9
DANN	Benign	0.93
PhyloP100		-0.047
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: rs2354037; hg19: chrX-122581202;