chrX-123239256-C-T

Variant summary

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

The NM_000828.5(GRIA3):​c.269-14047C>T 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 0.76 ( 22829 hom., 23658 hem., cov: 21)
Failed GnomAD Quality Control

Consequence

GRIA3
NM_000828.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.199

Publications

4 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

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=-0.84).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GRIA3NM_000828.5 linkc.269-14047C>T intron_variant Intron 2 of 15 ENST00000622768.5 NP_000819.4 P42263-1Q17R51
GRIA3NM_007325.5 linkc.269-14047C>T intron_variant Intron 2 of 15 ENST00000620443.2 NP_015564.5 P42263-2Q17R51

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GRIA3ENST00000620443.2 linkc.269-14047C>T intron_variant Intron 2 of 15 1 NM_007325.5 ENSP00000478489.1 P42263-2
GRIA3ENST00000622768.5 linkc.269-14047C>T intron_variant Intron 2 of 15 5 NM_000828.5 ENSP00000481554.1 P42263-1

Frequencies

GnomAD3 genomes
AF:
0.757
AC:
82101
AN:
108480
Hom.:
22826
Cov.:
21
show subpopulations
Gnomad AFR
AF:
0.851
Gnomad AMI
AF:
0.810
Gnomad AMR
AF:
0.840
Gnomad ASJ
AF:
0.741
Gnomad EAS
AF:
0.894
Gnomad SAS
AF:
0.815
Gnomad FIN
AF:
0.663
Gnomad MID
AF:
0.766
Gnomad NFE
AF:
0.684
Gnomad OTH
AF:
0.767
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:
0.757
AC:
82144
AN:
108530
Hom.:
22829
Cov.:
21
AF XY:
0.757
AC XY:
23658
AN XY:
31264
show subpopulations
African (AFR)
AF:
0.851
AC:
25640
AN:
30144
American (AMR)
AF:
0.841
AC:
8581
AN:
10207
Ashkenazi Jewish (ASJ)
AF:
0.741
AC:
1889
AN:
2549
East Asian (EAS)
AF:
0.894
AC:
3066
AN:
3428
South Asian (SAS)
AF:
0.815
AC:
1985
AN:
2435
European-Finnish (FIN)
AF:
0.663
AC:
3747
AN:
5648
Middle Eastern (MID)
AF:
0.759
AC:
145
AN:
191
European-Non Finnish (NFE)
AF:
0.684
AC:
35410
AN:
51780
Other (OTH)
AF:
0.770
AC:
1140
AN:
1480
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
681
1361
2042
2722
3403
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
678
1356
2034
2712
3390
<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:
0.715
Hom.:
46684
Bravo
AF:
0.782

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
1.3
DANN
Benign
0.84
PhyloP100
-0.20
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

Publications

Other links and lift over

dbSNP: rs989638; hg19: chrX-122373107; API