chrX-123184533-A-AG

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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:5
• Conservation: PhyloP100: 6.32

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]

ACMG classification

Verdict is Likely_benign. Variant got -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 id is 167157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA3	NM_000828.5	c.-2dupG		start_retained_variant	Exon 1 of 16	ENST00000622768.5	NP_000819.4
GRIA3	NM_007325.5	c.-2dupG		start_retained_variant	Exon 1 of 16	ENST00000620443.2	NP_015564.5
GRIA3	NM_000828.5	c.-2dupG		5_prime_UTR_variant	Exon 1 of 16	ENST00000622768.5	NP_000819.4
GRIA3	NM_007325.5	c.-2dupG		5_prime_UTR_variant	Exon 1 of 16	ENST00000620443.2	NP_015564.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIA3	ENST00000620443	c.-2dupG		start_retained_variant	Exon 1 of 16	1	NM_007325.5	ENSP00000478489.1
GRIA3	ENST00000622768	c.-2dupG		start_retained_variant	Exon 1 of 16	5	NM_000828.5	ENSP00000481554.1
GRIA3	ENST00000620443	c.-2dupG		5_prime_UTR_variant	Exon 1 of 16	1	NM_007325.5	ENSP00000478489.1
GRIA3	ENST00000622768	c.-2dupG		5_prime_UTR_variant	Exon 1 of 16	5	NM_000828.5	ENSP00000481554.1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD3 exomes AF: 1.00 AC: 183515 AN: 183516 Hom.: 57785 AF XY: 1.00 AC XY: 67944 AN XY: 67944

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 SAS 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

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 19, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 03, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Aug 14, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Syndromic X-linked intellectual disability 94 Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases Benign:1

Nov 24, 2014

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs58044961; hg19: chrX-122318386;