NM_000828.5:c.2076+17114A>C

Variant names:

• chrX-123445253-A-C
• rs687577
• NM_000828.5:c.2076+17114A>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.2076+17114A>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 0.82 (26376 hom., 26718 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: GRIA3 NM_000828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• 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, 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=-0.94).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA3	NM_000828.5	c.2076+17114A>C		intron_variant	Intron 12 of 15	ENST00000622768.5	NP_000819.4
GRIA3	NM_007325.5	c.2076+17114A>C		intron_variant	Intron 12 of 15	ENST00000620443.2	NP_015564.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIA3	ENST00000620443.2	c.2076+17114A>C		intron_variant	Intron 12 of 15	1	NM_007325.5	ENSP00000478489.1
GRIA3	ENST00000622768.5	c.2076+17114A>C		intron_variant	Intron 12 of 15	5	NM_000828.5	ENSP00000481554.1

Frequencies

GnomAD3 genomes AF: 0.819 AC: 90394 AN: 110418 Hom.: 26383 Cov.: 23

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.933

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.878

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.884

Gnomad OTH AF: 0.815

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: 0.819 AC: 90425 AN: 110471 Hom.: 26376 Cov.: 23 AF XY: 0.817 AC XY: 26718 AN XY: 32713

African (AFR) AF: 0.703 AC: 21349 AN: 30359

American (AMR) AF: 0.836 AC: 8706 AN: 10420

Ashkenazi Jewish (ASJ) AF: 0.856 AC: 2256 AN: 2634

East Asian (EAS) AF: 0.701 AC: 2438 AN: 3476

South Asian (SAS) AF: 0.730 AC: 1856 AN: 2541

European-Finnish (FIN) AF: 0.878 AC: 5135 AN: 5846

Middle Eastern (MID) AF: 0.837 AC: 180 AN: 215

European-Non Finnish (NFE) AF: 0.884 AC: 46650 AN: 52792

Other (OTH) AF: 0.809 AC: 1218 AN: 1505

Alfa AF: 0.857 Hom.: 94924

Bravo AF: 0.815

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.082
DANN	Benign	0.33
PhyloP100		-1.3
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: rs687577; hg19: chrX-122579104;