rs549895

Variant names:

• chrX-123409775-T-C
• rs549895
• NM_000828.5:c.1500+4861T>C

Variant summary

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

The NM_000828.5(GRIA3):​c.1500+4861T>C 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 0.55 (12176 hom., 18010 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: GRIA3 NM_000828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520
• 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=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA3	NM_000828.5	c.1500+4861T>C		intron_variant	Intron 10 of 15	ENST00000622768.5	NP_000819.4
GRIA3	NM_007325.5	c.1500+4861T>C		intron_variant	Intron 10 of 15	ENST00000620443.2	NP_015564.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIA3	ENST00000620443.2	c.1500+4861T>C		intron_variant	Intron 10 of 15	1	NM_007325.5	ENSP00000478489.1
GRIA3	ENST00000622768.5	c.1500+4861T>C		intron_variant	Intron 10 of 15	5	NM_000828.5	ENSP00000481554.1

Frequencies

GnomAD3 genomes AF: 0.554 AC: 60973 AN: 110028 Hom.: 12181 Cov.: 22

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.645

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.541

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: 0.554 AC: 60994 AN: 110080 Hom.: 12176 Cov.: 22 AF XY: 0.556 AC XY: 18010 AN XY: 32380

African (AFR) AF: 0.418 AC: 12659 AN: 30278

American (AMR) AF: 0.571 AC: 5908 AN: 10352

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 1702 AN: 2629

East Asian (EAS) AF: 0.637 AC: 2194 AN: 3444

South Asian (SAS) AF: 0.445 AC: 1136 AN: 2550

European-Finnish (FIN) AF: 0.723 AC: 4174 AN: 5777

Middle Eastern (MID) AF: 0.640 AC: 137 AN: 214

European-Non Finnish (NFE) AF: 0.604 AC: 31812 AN: 52673

Other (OTH) AF: 0.547 AC: 819 AN: 1497

Alfa AF: 0.577 Hom.: 21397

Bravo AF: 0.546

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.81
DANN	Benign	0.43
PhyloP100		-0.052
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: rs549895; hg19: chrX-122543626;