rs58044961

Variant names:

• chrX-123184533-A-AG
• rs58044961
• NM_000828.5:c.-2dupG

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM2 BP6_Very_Strong

The NM_007325.5(GRIA3):​c.-2dupG variant causes a start retained change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: not found (cov: 21)
• Consequence: GRIA3 NM_007325.5 start_retained
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 6.32
• Publications: 8 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant X-123184533-A-AG is Benign according to our data. Variant chrX-123184533-A-AG is described in ClinVar as Benign. ClinVar VariationId is 167157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.-2dupG		start_retained	Exon 1 of 16	NP_000819.4	P42263-1
	GRIA3	NM_007325.5	MANE Select	c.-2dupG		start_retained	Exon 1 of 16	NP_015564.5
	GRIA3	NM_000828.5	MANE Plus Clinical	c.-2dupG		5_prime_UTR	Exon 1 of 16	NP_000819.4	P42263-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA3	ENST00000620443.2	TSL:1 MANE Select	c.-2dupG		start_retained	Exon 1 of 16	ENSP00000478489.1	P42263-2
	GRIA3	ENST00000622768.5	TSL:5 MANE Plus Clinical	c.-2dupG		start_retained	Exon 1 of 16	ENSP00000481554.1	P42263-1
	GRIA3	ENST00000611689.4	TSL:1	c.-2dupG		start_retained	Exon 1 of 4	ENSP00000478758.1	Q5XKG2

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD2 exomes AF: 1.00 AC: 183515 AN: 183516 AF XY: 1.00

Gnomad AFR exome AF: 1.00

Gnomad AMR exome AF: 1.00

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 1.00

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 21

Alfa AF: 0.491 Hom.: 6764

Asia WGS AF: 1.00 AC: 2522 AN: 2522

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Inborn genetic diseases (1)
-	-	1	Syndromic X-linked intellectual disability 94 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs58044961; hg19: chrX-122318386;