Variant chr9-101686816-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_133445.3(GRIN3A):c.1084G>A(p.Val362Met) variant causes a missense change. The variant allele was found at a frequency of 0.305 in 1,613,836 control chromosomes in the GnomAD database, including 78,150 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.35 ( 10213 hom., cov: 33)

Exomes 𝑓: 0.30 ( 67937 hom. )

Consequence

GRIN3A
NM_133445.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.05

Variant links:

Genes affected

GRIN3A (HGNC:16767): (glutamate ionotropic receptor NMDA type subunit 3A) This gene encodes a subunit of the N-methyl-D-aspartate (NMDA) receptors, which belong to the superfamily of glutamate-regulated ion channels, and function in physiological and pathological processes in the central nervous system. This subunit shows greater than 90% identity to the corresponding subunit in rat. Studies in the knockout mouse deficient in this subunit suggest that this gene may be involved in the development of synaptic elements by modulating NMDA receptor activity. [provided by RefSeq, Jul 2008]

GRIN3A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021012723).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN3A	NM_133445.3 link	c.1084G>A	p.Val362Met	missense_variant	Exon 2 of 9	ENST00000361820.6	NP_597702.2	Q8TCU5
GRIN3A	XM_011518211.3 link	c.1084G>A	p.Val362Met	missense_variant	Exon 2 of 7		XP_011516513.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN3A	ENST00000361820.6 link	c.1084G>A	p.Val362Met	missense_variant	Exon 2 of 9	1	NM_133445.3	ENSP00000355155.3		Q8TCU5

Frequencies

GnomAD3 genomes

AF:

0.354

AC:

53795

AN:

152028

Hom.:

10182

Cov.:

show subpopulations

Gnomad AFR

AF:

0.480

Gnomad AMI

AF:

0.310

Gnomad AMR

AF:

0.309

Gnomad ASJ

AF:

0.368

Gnomad EAS

AF:

0.100

Gnomad SAS

AF:

0.272

Gnomad FIN

AF:

0.347

Gnomad MID

AF:

0.434

Gnomad NFE

AF:

0.313

Gnomad OTH

AF:

0.347

GnomAD3 exomes

AF:

0.298

AC:

74763

AN:

251098

Hom.:

12085

AF XY:

0.298

AC XY:

40454

AN XY:

135692

show subpopulations

Gnomad AFR exome

AF:

0.485

Gnomad AMR exome

AF:

0.249

Gnomad ASJ exome

AF:

0.352

Gnomad EAS exome

AF:

0.0833

Gnomad SAS exome

AF:

0.295

Gnomad FIN exome

AF:

0.342

Gnomad NFE exome

AF:

0.308

Gnomad OTH exome

AF:

0.307

GnomAD4 exome

AF:

0.300

AC:

438920

AN:

1461690

Hom.:

67937

Cov.:

AF XY:

0.301

AC XY:

218747

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.490

Gnomad4 AMR exome

AF:

0.255

Gnomad4 ASJ exome

AF:

0.354

Gnomad4 EAS exome

AF:

0.169

Gnomad4 SAS exome

AF:

0.293

Gnomad4 FIN exome

AF:

0.338

Gnomad4 NFE exome

AF:

0.298

Gnomad4 OTH exome

AF:

0.308

GnomAD4 genome

AF:

0.354

AC:

53880

AN:

152146

Hom.:

10213

Cov.:

AF XY:

0.352

AC XY:

26208

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.481

Gnomad4 AMR

AF:

0.308

Gnomad4 ASJ

AF:

0.368

Gnomad4 EAS

AF:

0.100

Gnomad4 SAS

AF:

0.273

Gnomad4 FIN

AF:

0.347

Gnomad4 NFE

AF:

0.313

Gnomad4 OTH

AF:

0.351

Alfa

AF:

0.310

Hom.:

18847

Bravo

AF:

0.352

TwinsUK

AF:

0.300

AC:

1111

ALSPAC

AF:

0.283

AC:

1090

ESP6500AA

AF:

0.475

AC:

2091

ESP6500EA

AF:

0.314

AC:

2703

ExAC

AF:

0.304

AC:

36868

Asia WGS

AF:

0.240

AC:

837

AN:

3478

EpiCase

AF:

0.308

EpiControl

AF:

0.302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.052

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.71

MetaRNN

Benign

0.0021

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.61

REVEL

Uncertain

0.41

Sift

Uncertain

0.025

Sift4G

Benign

0.12

Polyphen

0.43

Vest4

0.22

MPC

0.28

ClinPred

0.041

GERP RS

5.8

Varity_R

0.22

gMVP

0.58

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over