rs5958217

Variant names:

• chrX-123296271-G-A
• rs5958217
• NM_000828.5:c.509-29755G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-123296271-G-A
• chrX-123296271-G-C
• chrX-123296271-G-T

Variant summary

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

The NM_000828.5(GRIA3):​c.509-29755G>A 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 0.77 (22642 hom., 24861 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: GRIA3 NM_000828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA3	NM_000828.5	c.509-29755G>A		intron_variant	Intron 3 of 15	ENST00000622768.5	NP_000819.4
GRIA3	NM_007325.5	c.509-29755G>A		intron_variant	Intron 3 of 15	ENST00000620443.2	NP_015564.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIA3	ENST00000620443.2	c.509-29755G>A		intron_variant	Intron 3 of 15	1	NM_007325.5	ENSP00000478489.1
GRIA3	ENST00000622768.5	c.509-29755G>A		intron_variant	Intron 3 of 15	5	NM_000828.5	ENSP00000481554.1
GRIA3	ENST00000620581.4	n.509-29755G>A		intron_variant	Intron 3 of 16	1		ENSP00000481875.1
ENSG00000307341	ENST00000825206.1	n.667+17574C>T		intron_variant	Intron 6 of 6

Frequencies

GnomAD3 genomes AF: 0.767 AC: 84017 AN: 109563 Hom.: 22655 Cov.: 23

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.934

Gnomad SAS AF: 0.877

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.825

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.766

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: 0.767 AC: 84049 AN: 109613 Hom.: 22642 Cov.: 23 AF XY: 0.773 AC XY: 24861 AN XY: 32159

African (AFR) AF: 0.723 AC: 21863 AN: 30257

American (AMR) AF: 0.807 AC: 8257 AN: 10226

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 2137 AN: 2622

East Asian (EAS) AF: 0.934 AC: 3232 AN: 3460

South Asian (SAS) AF: 0.876 AC: 2251 AN: 2569

European-Finnish (FIN) AF: 0.760 AC: 4407 AN: 5798

Middle Eastern (MID) AF: 0.822 AC: 176 AN: 214

European-Non Finnish (NFE) AF: 0.766 AC: 40037 AN: 52285

Other (OTH) AF: 0.769 AC: 1157 AN: 1505

Alfa AF: 0.773 Hom.: 37487

Bravo AF: 0.772

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.6
DANN	Benign	0.80
PhyloP100		-0.019
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: rs5958217; hg19: chrX-122430122;