rs5911622

Variant names:

• chrX-123449072-T-C
• rs5911622
• NM_000828.5:c.2077-15793T>C

Variant summary

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

The NM_007325.5(GRIA3):​c.2077-15793T>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 0.52 (10650 hom., 16710 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: GRIA3 NM_007325.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.977
• Publications: 3 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, G2P, Labcorp Genetics (formerly Invitae)
• 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=-0.92).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007325.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA3	NM_000828.5	MANE Plus Clinical	c.2077-15793T>C		intron	N/A	NP_000819.4	P42263-1
	GRIA3	NM_007325.5	MANE Select	c.2077-15793T>C		intron	N/A	NP_015564.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA3	ENST00000620443.2	TSL:1 MANE Select	c.2077-15793T>C		intron	N/A	ENSP00000478489.1	P42263-2
	GRIA3	ENST00000622768.5	TSL:5 MANE Plus Clinical	c.2077-15793T>C		intron	N/A	ENSP00000481554.1	P42263-1
	GRIA3	ENST00000620581.4	TSL:1	n.2077-15793T>C		intron	N/A	ENSP00000481875.1	A0A087WYJ6

Frequencies

GnomAD3 genomes AF: 0.520 AC: 57329 AN: 110169 Hom.: 10660 Cov.: 22

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.531

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: 0.520 AC: 57344 AN: 110226 Hom.: 10650 Cov.: 22 AF XY: 0.514 AC XY: 16710 AN XY: 32540

African (AFR) AF: 0.510 AC: 15447 AN: 30270

American (AMR) AF: 0.556 AC: 5753 AN: 10356

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1484 AN: 2622

East Asian (EAS) AF: 0.413 AC: 1430 AN: 3460

South Asian (SAS) AF: 0.400 AC: 1034 AN: 2584

European-Finnish (FIN) AF: 0.544 AC: 3150 AN: 5790

Middle Eastern (MID) AF: 0.568 AC: 121 AN: 213

European-Non Finnish (NFE) AF: 0.526 AC: 27733 AN: 52752

Other (OTH) AF: 0.525 AC: 796 AN: 1517

Alfa AF: 0.530 Hom.: 79925

Bravo AF: 0.525

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.52
DANN	Benign	0.73
PhyloP100		-0.98
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs5911622;

hg19: chrX-122582923;

COSMIC: COSV52062156;