rs524654

Variant names:

• chrX-123437079-A-C
• rs524654
• NM_000828.5:c.2076+8940A>C

Your query was ambiguous. Multiple possible variants found:

• chrX-123437079-A-C
• chrX-123437079-A-G

Variant summary

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

The NM_007325.5(GRIA3):​c.2076+8940A>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 0.78 (24125 hom., 22966 hem., cov: 21)
  • Failed GnomAD Quality Control
• Consequence: GRIA3 NM_007325.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139
• 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, 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=-0.98).

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.2076+8940A>C		intron	N/A	NP_000819.4	P42263-1
	GRIA3	NM_007325.5	MANE Select	c.2076+8940A>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.2076+8940A>C		intron	N/A	ENSP00000478489.1	P42263-2
	GRIA3	ENST00000622768.5	TSL:5 MANE Plus Clinical	c.2076+8940A>C		intron	N/A	ENSP00000481554.1	P42263-1
	GRIA3	ENST00000620581.4	TSL:1	n.2076+8940A>C		intron	N/A	ENSP00000481875.1	A0A087WYJ6

Frequencies

GnomAD3 genomes AF: 0.785 AC: 84042 AN: 107090 Hom.: 24131 Cov.: 21

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.900

Gnomad AMR AF: 0.816

Gnomad ASJ AF: 0.854

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.754

Gnomad NFE AF: 0.825

Gnomad OTH AF: 0.777

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: 0.785 AC: 84062 AN: 107144 Hom.: 24125 Cov.: 21 AF XY: 0.775 AC XY: 22966 AN XY: 29622

African (AFR) AF: 0.716 AC: 21101 AN: 29458

American (AMR) AF: 0.816 AC: 7845 AN: 9614

Ashkenazi Jewish (ASJ) AF: 0.854 AC: 2207 AN: 2584

East Asian (EAS) AF: 0.707 AC: 2390 AN: 3382

South Asian (SAS) AF: 0.722 AC: 1726 AN: 2390

European-Finnish (FIN) AF: 0.747 AC: 3997 AN: 5351

Middle Eastern (MID) AF: 0.754 AC: 159 AN: 211

European-Non Finnish (NFE) AF: 0.825 AC: 42903 AN: 52021

Other (OTH) AF: 0.772 AC: 1121 AN: 1452

Alfa AF: 0.811 Hom.: 36476

Bravo AF: 0.790

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.68
DANN	Benign	0.55
PhyloP100		-0.14
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: rs524654; hg19: chrX-122570930;