rs6608062

Variant names:

• chrX-123234050-G-A
• rs6608062
• NM_000828.5:c.269-19253G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-123234050-G-A
• chrX-123234050-G-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.269-19253G>A 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 0.59 (14142 hom., 19254 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: GRIA3 NM_000828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.644
• Publications: 2 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=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000828.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA3	NM_000828.5	MANE Plus Clinical	c.269-19253G>A		intron	N/A	NP_000819.4
	GRIA3	NM_007325.5	MANE Select	c.269-19253G>A		intron	N/A	NP_015564.5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA3	ENST00000620443.2	TSL:1 MANE Select	c.269-19253G>A		intron	N/A	ENSP00000478489.1
	GRIA3	ENST00000622768.5	TSL:5 MANE Plus Clinical	c.269-19253G>A		intron	N/A	ENSP00000481554.1
	GRIA3	ENST00000620581.4	TSL:1	n.269-19253G>A		intron	N/A	ENSP00000481875.1

Frequencies

GnomAD3 genomes AF: 0.590 AC: 64770 AN: 109691 Hom.: 14139 Cov.: 22

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.678

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.614

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: 0.590 AC: 64792 AN: 109744 Hom.: 14142 Cov.: 22 AF XY: 0.599 AC XY: 19254 AN XY: 32132

African (AFR) AF: 0.397 AC: 12002 AN: 30233

American (AMR) AF: 0.739 AC: 7603 AN: 10290

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 1707 AN: 2615

East Asian (EAS) AF: 0.977 AC: 3377 AN: 3457

South Asian (SAS) AF: 0.808 AC: 2004 AN: 2479

European-Finnish (FIN) AF: 0.606 AC: 3525 AN: 5816

Middle Eastern (MID) AF: 0.676 AC: 144 AN: 213

European-Non Finnish (NFE) AF: 0.632 AC: 33186 AN: 52479

Other (OTH) AF: 0.619 AC: 924 AN: 1493

Alfa AF: 0.627 Hom.: 60842

Bravo AF: 0.596

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.48
PhyloP100		0.64
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: rs6608062; hg19: chrX-122367901;