NM_000828.5:c.1200T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_000828.5(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_000828.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.14

Publications

20 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
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: Benign. The variant received -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 VariationId is 129167.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.14 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000828.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA3	NM_000828.5	MANE Plus Clinical	c.1200T>C	p.Asn400Asn	synonymous	Exon 9 of 16	NP_000819.4	P42263-1
	GRIA3	NM_007325.5	MANE Select	c.1200T>C	p.Asn400Asn	synonymous	Exon 9 of 16	NP_015564.5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GRIA3	ENST00000620443.2	TSL:1 MANE Select	c.1200T>C	p.Asn400Asn	synonymous	Exon 9 of 16	ENSP00000478489.1	P42263-2
GRIA3	ENST00000622768.5	TSL:5 MANE Plus Clinical	c.1200T>C	p.Asn400Asn	synonymous	Exon 9 of 16	ENSP00000481554.1	P42263-1
GRIA3	ENST00000620581.4	TSL:1	n.1200T>C		non_coding_transcript_exon	Exon 9 of 17	ENSP00000481875.1	A0A087WYJ6

Frequencies

GnomAD3 genomes

AF:

0.559

AC:

61905

AN:

110644

Hom.:

12341

Cov.:

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

GnomAD2 exomes

AF:

0.587

AC:

107501

AN:

183055

AF XY:

0.587

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 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

African (AFR)

AF:

0.439

AC:

11302

AN:

25766

American (AMR)

AF:

0.559

AC:

19646

AN:

35138

Ashkenazi Jewish (ASJ)

AF:

0.640

AC:

12210

AN:

19087

East Asian (EAS)

AF:

0.665

AC:

19969

AN:

30029

South Asian (SAS)

AF:

0.461

AC:

24586

AN:

53368

European-Finnish (FIN)

AF:

0.726

AC:

29414

AN:

40517

Middle Eastern (MID)

AF:

0.607

AC:

2451

AN:

4038

European-Non Finnish (NFE)

AF:

0.599

AC:

484820

AN:

808807

Other (OTH)

AF:

0.581

AC:

26068

AN:

44882

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

8018

16036

24055

32073

40091

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14544

29088

43632

58176

72720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

African (AFR)

AF:

0.436

AC:

13276

AN:

30480

American (AMR)

AF:

0.572

AC:

5972

AN:

10438

Ashkenazi Jewish (ASJ)

AF:

0.644

AC:

1690

AN:

2624

East Asian (EAS)

AF:

0.636

AC:

2202

AN:

3463

South Asian (SAS)

AF:

0.450

AC:

1168

AN:

2593

European-Finnish (FIN)

AF:

0.730

AC:

4332

AN:

5936

Middle Eastern (MID)

AF:

0.633

AC:

133

AN:

210

European-Non Finnish (NFE)

AF:

0.604

AC:

31878

AN:

52777

Other (OTH)

AF:

0.554

AC:

837

AN:

1510

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

967

1933

2900

3866

4833

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

564

1128

1692

2256

2820

<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:

0.574

Hom.:

44959

Bravo

AF:

0.551

EpiCase

AF:

0.608

EpiControl

AF:

0.614

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Inborn genetic diseases (1)

Syndromic X-linked intellectual disability 94 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.1

Mutation Taster

=95/5

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over