rs502434

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_007325.5(GRIA3):c.1200T>C(p.Asn400Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 12338 hom., 18554 hem., cov: 23)

Exomes 𝑓: 0.59 ( 130711 hom. 197798 hem. )

Failed GnomAD Quality Control

Consequence

GRIA3
NM_007325.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.14

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant X-123403426-T-C is Benign according to our data. Variant chrX-123403426-T-C is described in ClinVar as [Benign]. Clinvar id is 129167.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-123403426-T-C is described in Lovd as [Benign]. Variant chrX-123403426-T-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.14 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA3	NM_000828.5 link	c.1200T>C	p.Asn400Asn	synonymous_variant	Exon 9 of 16	ENST00000622768.5	NP_000819.4	P42263-1Q17R51
GRIA3	NM_007325.5 link	c.1200T>C	p.Asn400Asn	synonymous_variant	Exon 9 of 16	ENST00000620443.2	NP_015564.5	P42263-2Q17R51

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GRIA3	ENST00000620443.2 link	c.1200T>C	p.Asn400Asn	synonymous_variant	Exon 9 of 16	1	NM_007325.5	ENSP00000478489.1	P42263-2
GRIA3	ENST00000622768.5 link	c.1200T>C	p.Asn400Asn	synonymous_variant	Exon 9 of 16	5	NM_000828.5	ENSP00000481554.1	P42263-1
GRIA3	ENST00000620581.4 link	n.1200T>C		non_coding_transcript_exon_variant	Exon 9 of 17	1		ENSP00000481875.1	A0A087WYJ6

Frequencies

GnomAD3 genomes

AF:

0.559

AC:

61905

AN:

110644

Hom.:

12341

Cov.:

AF XY:

0.563

AC XY:

18520

AN XY:

32906

show subpopulations

Gnomad AFR

AF:

0.436

Gnomad AMI

AF:

0.665

Gnomad AMR

AF:

0.572

Gnomad ASJ

AF:

0.644

Gnomad EAS

AF:

0.637

Gnomad SAS

AF:

0.448

Gnomad FIN

AF:

0.730

Gnomad MID

AF:

0.639

Gnomad NFE

AF:

0.604

Gnomad OTH

AF:

0.548

GnomAD3 exomes

AF:

0.587

AC:

107501

AN:

183055

Hom.:

20189

AF XY:

0.587

AC XY:

39666

AN XY:

67617

show subpopulations

Gnomad AFR exome

AF:

0.437

Gnomad AMR exome

AF:

0.560

Gnomad ASJ exome

AF:

0.638

Gnomad EAS exome

AF:

0.611

Gnomad SAS exome

AF:

0.459

Gnomad FIN exome

AF:

0.737

Gnomad NFE exome

AF:

0.612

Gnomad OTH exome

AF:

0.602

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.594

AC:

630466

AN:

1061632

Hom.:

130711

Cov.:

AF XY:

0.585

AC XY:

197798

AN XY:

338076

show subpopulations

Gnomad4 AFR exome

AF:

0.439

Gnomad4 AMR exome

AF:

0.559

Gnomad4 ASJ exome

AF:

0.640

Gnomad4 EAS exome

AF:

0.665

Gnomad4 SAS exome

AF:

0.461

Gnomad4 FIN exome

AF:

0.726

Gnomad4 NFE exome

AF:

0.599

Gnomad4 OTH exome

AF:

0.581

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.559

AC:

61934

AN:

110702

Hom.:

12338

Cov.:

AF XY:

0.563

AC XY:

18554

AN XY:

32974

show subpopulations

Gnomad4 AFR

AF:

0.436

Gnomad4 AMR

AF:

0.572

Gnomad4 ASJ

AF:

0.644

Gnomad4 EAS

AF:

0.636

Gnomad4 SAS

AF:

0.450

Gnomad4 FIN

AF:

0.730

Gnomad4 NFE

AF:

0.604

Gnomad4 OTH

AF:

0.554

Alfa

AF:

0.597

Hom.:

29059

Bravo

AF:

0.551

EpiCase

AF:

0.608

EpiControl

AF:

0.614

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

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

Jun 22, 2015

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

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

6.3

DANN

Benign

0.72

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over