rs5911556

Variant names:

• chrX-123232086-C-A
• rs5911556
• NM_000828.5:c.269-21217C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000828.5(GRIA3):​c.269-21217C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0174 in 111,508 control chromosomes in the GnomAD database, including 24 homozygotes. There are 517 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 0.017 (24 hom., 517 hem., cov: 23)
• Consequence: GRIA3 NM_000828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103
• 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=-0.78).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0174 (1940/111508) while in subpopulation NFE AF = 0.0266 (1412/53026). AF 95% confidence interval is 0.0255. There are 24 homozygotes in GnomAd4. There are 517 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 24 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA3	NM_000828.5	c.269-21217C>A		intron_variant	Intron 2 of 15	ENST00000622768.5	NP_000819.4
GRIA3	NM_007325.5	c.269-21217C>A		intron_variant	Intron 2 of 15	ENST00000620443.2	NP_015564.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIA3	ENST00000620443.2	c.269-21217C>A		intron_variant	Intron 2 of 15	1	NM_007325.5	ENSP00000478489.1
GRIA3	ENST00000622768.5	c.269-21217C>A		intron_variant	Intron 2 of 15	5	NM_000828.5	ENSP00000481554.1

Frequencies

GnomAD3 genomes AF: 0.0174 AC: 1939 AN: 111454 Hom.: 23 Cov.: 23

Gnomad AFR AF: 0.00378

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0121

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00114

Gnomad FIN AF: 0.0344

Gnomad MID AF: 0.00847

Gnomad NFE AF: 0.0266

Gnomad OTH AF: 0.0187

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

GnomAD4 genome AF: 0.0174 AC: 1940 AN: 111508 Hom.: 24 Cov.: 23 AF XY: 0.0153 AC XY: 517 AN XY: 33822

African (AFR) AF: 0.00378 AC: 116 AN: 30725

American (AMR) AF: 0.0122 AC: 128 AN: 10510

Ashkenazi Jewish (ASJ) AF: 0.0167 AC: 44 AN: 2635

East Asian (EAS) AF: 0.00 AC: 0 AN: 3548

South Asian (SAS) AF: 0.00114 AC: 3 AN: 2628

European-Finnish (FIN) AF: 0.0344 AC: 207 AN: 6016

Middle Eastern (MID) AF: 0.00930 AC: 2 AN: 215

European-Non Finnish (NFE) AF: 0.0266 AC: 1412 AN: 53026

Other (OTH) AF: 0.0184 AC: 28 AN: 1521

Alfa AF: 0.0222 Hom.: 270

Bravo AF: 0.0155

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.7
DANN	Benign	0.65
PhyloP100		-0.10
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: rs5911556; hg19: chrX-122365937;