dbSNP rs2157292: GRIA3:c.269-32471G>A (chrX-123220832-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The NM_000828.5(GRIA3):c.269-32471G>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 0.75 ( 23227 hom., 24569 hem., cov: 22)

Failed GnomAD Quality Control

Consequence

GRIA3
NM_000828.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.38

Publications

0 publications found

Variant links:

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

GRIA3 links:

ENSG00000307341 (HGNC:):

ENSG00000307341 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA3	NM_000828.5 link	c.269-32471G>A		intron_variant	Intron 2 of 15	ENST00000622768.5	NP_000819.4
GRIA3	NM_007325.5 link	c.269-32471G>A		intron_variant	Intron 2 of 15	ENST00000620443.2	NP_015564.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIA3	ENST00000620443.2 link	c.269-32471G>A		intron_variant	Intron 2 of 15	1	NM_007325.5	ENSP00000478489.1
GRIA3	ENST00000622768.5 link	c.269-32471G>A		intron_variant	Intron 2 of 15	5	NM_000828.5	ENSP00000481554.1

Frequencies

GnomAD3 genomes

AF:

0.754

AC:

83098

AN:

110190

Hom.:

23246

Cov.:

show subpopulations

Gnomad AFR

AF:

0.488

Gnomad AMI

AF:

0.909

Gnomad AMR

AF:

0.748

Gnomad ASJ

AF:

0.881

Gnomad EAS

AF:

0.902

Gnomad SAS

AF:

0.785

Gnomad FIN

AF:

0.850

Gnomad MID

AF:

0.803

Gnomad NFE

AF:

0.877

Gnomad OTH

AF:

0.760

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:

0.754

AC:

83111

AN:

110247

Hom.:

23227

Cov.:

AF XY:

0.756

AC XY:

24569

AN XY:

32495

show subpopulations

African (AFR)

AF:

0.488

AC:

14786

AN:

30300

American (AMR)

AF:

0.748

AC:

7753

AN:

10361

Ashkenazi Jewish (ASJ)

AF:

0.881

AC:

2307

AN:

2619

East Asian (EAS)

AF:

0.902

AC:

3133

AN:

3473

South Asian (SAS)

AF:

0.781

AC:

1997

AN:

2556

European-Finnish (FIN)

AF:

0.850

AC:

4912

AN:

5779

Middle Eastern (MID)

AF:

0.785

AC:

168

AN:

214

European-Non Finnish (NFE)

AF:

0.878

AC:

46308

AN:

52772

Other (OTH)

AF:

0.756

AC:

1129

AN:

1493

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

613

1226

1840

2453

3066

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

706

1412

2118

2824

3530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.822

Hom.:

94859

Bravo

AF:

0.737

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.053

(source)

DANN

Benign

0.75

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over