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rs145583732

chrX-123185881-T-CchrX-123185881-T-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000828.5(GRIA3):c.159T>C(p.Phe53=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,205,559 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 390 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00084 ( 0 hom., 29 hem., cov: 22)
Exomes 𝑓: 0.0010 ( 0 hom. 361 hem. )

Consequence

GRIA3
NM_000828.5 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:4

Conservation

PhyloP100: 2.36
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant X-123185881-T-C is Benign according to our data. Variant chrX-123185881-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 435359.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-123185881-T-C is described in Lovd as [Likely_benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2.36 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000843 (94/111487) while in subpopulation NFE AF= 0.00119 (63/53066). AF 95% confidence interval is 0.000951. There are 0 homozygotes in gnomad4. There are 29 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Hemizygotes in GnomAd at 29 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GRIA3NM_000828.5 linkuse as main transcriptc.159T>C p.Phe53= synonymous_variant 2/16 ENST00000622768.5
GRIA3NM_007325.5 linkuse as main transcriptc.159T>C p.Phe53= synonymous_variant 2/16 ENST00000620443.2
GRIA3NM_001256743.2 linkuse as main transcriptc.159T>C p.Phe53= synonymous_variant 2/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GRIA3ENST00000620443.2 linkuse as main transcriptc.159T>C p.Phe53= synonymous_variant 2/161 NM_007325.5 P4P42263-2
GRIA3ENST00000622768.5 linkuse as main transcriptc.159T>C p.Phe53= synonymous_variant 2/165 NM_000828.5 A1P42263-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000843
AC:
94
AN:
111487
Hom.:
0
Cov.:
22
AF XY:
0.000862
AC XY:
29
AN XY:
33655
show subpopulations
Gnomad AFR
AF:
0.000164
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00426
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00119
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000873
AC:
160
AN:
183339
Hom.:
0
AF XY:
0.000752
AC XY:
51
AN XY:
67799
show subpopulations
Gnomad AFR exome
AF:
0.0000762
Gnomad AMR exome
AF:
0.0000729
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00407
Gnomad NFE exome
AF:
0.00110
Gnomad OTH exome
AF:
0.000441
GnomAD4 exome
AF:
0.00102
AC:
1118
AN:
1094072
Hom.:
0
Cov.:
30
AF XY:
0.00100
AC XY:
361
AN XY:
359536
show subpopulations
Gnomad4 AFR exome
AF:
0.000114
Gnomad4 AMR exome
AF:
0.0000568
Gnomad4 ASJ exome
AF:
0.0000517
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00422
Gnomad4 NFE exome
AF:
0.00108
Gnomad4 OTH exome
AF:
0.000696
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000843
AC:
94
AN:
111487
Hom.:
0
Cov.:
22
AF XY:
0.000862
AC XY:
29
AN XY:
33655
show subpopulations
Gnomad4 AFR
AF:
0.000164
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00426
Gnomad4 NFE
AF:
0.00119
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00109
Hom.:
9
Bravo
AF:
0.000570
EpiCase
AF:
0.000654
EpiControl
AF:
0.000652

ClinVar

Significance: Benign/Likely benign
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Uncertain:1Benign:2
Benign, criteria provided, single submitterclinical testingInvitaeJan 29, 2024- -
Uncertain significance, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Benign, criteria provided, single submitterclinical testingGeneDxSep 15, 2020- -
not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoSep 03, 2015- -
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsAug 28, 2014This alteration is classified as likely 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

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.50
Cadd
Benign
13
Dann
Benign
0.75

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: rs145583732; hg19: chrX-122319733; API