X-123184592-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_007325.5(GRIA3):​c.57C>T​(p.Val19Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,677 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. 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: not found (cov: 20)
Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )

Consequence

GRIA3
NM_007325.5 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.74
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP7
Synonymous conserved (PhyloP=1.74 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GRIA3NM_000828.5 linkc.57C>T p.Val19Val synonymous_variant Exon 1 of 16 ENST00000622768.5 NP_000819.4 P42263-1Q17R51
GRIA3NM_007325.5 linkc.57C>T p.Val19Val synonymous_variant Exon 1 of 16 ENST00000620443.2 NP_015564.5 P42263-2Q17R51
GRIA3NM_001256743.2 linkc.57C>T p.Val19Val synonymous_variant Exon 1 of 4 NP_001243672.1 Q5XKG2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GRIA3ENST00000620443.2 linkc.57C>T p.Val19Val synonymous_variant Exon 1 of 16 1 NM_007325.5 ENSP00000478489.1 P42263-2
GRIA3ENST00000622768.5 linkc.57C>T p.Val19Val synonymous_variant Exon 1 of 16 5 NM_000828.5 ENSP00000481554.1 P42263-1

Frequencies

GnomAD3 genomes
Cov.:
20
GnomAD4 exome
AF:
9.12e-7
AC:
1
AN:
1096677
Hom.:
0
Cov.:
29
AF XY:
0.00000276
AC XY:
1
AN XY:
362083
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000119
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.46
CADD
Benign
14
DANN
Benign
0.61

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs896354134; hg19: chrX-122318444; API