rs5910001

Variant names:

• chrX-123375442-C-T
• rs5910001
• NM_000828.5:c.751-19526C>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.751-19526C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 110,783 control chromosomes in the GnomAD database, including 1,086 homozygotes. There are 4,741 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 0.15 (1086 hom., 4741 hem., cov: 23)
• Consequence: GRIA3 NM_000828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.921
• 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=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA3	NM_000828.5	c.751-19526C>T		intron_variant	Intron 5 of 15	ENST00000622768.5	NP_000819.4
GRIA3	NM_007325.5	c.751-19526C>T		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.751-19526C>T		intron_variant	Intron 5 of 15	1	NM_007325.5	ENSP00000478489.1
GRIA3	ENST00000622768.5	c.751-19526C>T		intron_variant	Intron 5 of 15	5	NM_000828.5	ENSP00000481554.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 16757 AN: 110731 Hom.: 1087 Cov.: 23

Gnomad AFR AF: 0.0897

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.0218

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.151 AC: 16756 AN: 110783 Hom.: 1086 Cov.: 23 AF XY: 0.143 AC XY: 4741 AN XY: 33129

African (AFR) AF: 0.0896 AC: 2736 AN: 30526

American (AMR) AF: 0.109 AC: 1139 AN: 10419

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 309 AN: 2617

East Asian (EAS) AF: 0.0219 AC: 78 AN: 3559

South Asian (SAS) AF: 0.135 AC: 358 AN: 2649

European-Finnish (FIN) AF: 0.190 AC: 1110 AN: 5848

Middle Eastern (MID) AF: 0.116 AC: 25 AN: 215

European-Non Finnish (NFE) AF: 0.202 AC: 10674 AN: 52769

Other (OTH) AF: 0.138 AC: 208 AN: 1505

Alfa AF: 0.183 Hom.: 4013

Bravo AF: 0.141

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.68
DANN	Benign	0.23
PhyloP100		-0.92
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: rs5910001; hg19: chrX-122509293;