Variant 9-101670973-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_133445.3(GRIN3A):c.1439G>A(p.Arg480His) variant causes a missense change. The variant allele was found at a frequency of 0.0194 in 1,613,932 control chromosomes in the GnomAD database, including 438 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 same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.017 ( 53 hom., cov: 33)

Exomes 𝑓: 0.020 ( 385 hom. )

Consequence

GRIN3A
NM_133445.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.08

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007731229).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.017 (2584/152220) while in subpopulation NFE AF= 0.0223 (1515/67992). AF 95% confidence interval is 0.0213. There are 53 homozygotes in gnomad4. There are 1385 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 53 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIN3A	NM_133445.3 linkuse as main transcript	c.1439G>A	p.Arg480His	missense_variant	3/9	ENST00000361820.6
GRIN3A	XM_011518211.3 linkuse as main transcript	c.1439G>A	p.Arg480His	missense_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN3A	ENST00000361820.6 linkuse as main transcript	c.1439G>A	p.Arg480His	missense_variant	3/9	1	NM_133445.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0170

AC:

2583

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00386

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0104

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.0615

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0223

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.0183

AC:

4594

AN:

251268

Hom.:

AF XY:

0.0186

AC XY:

2531

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.00388

Gnomad AMR exome

AF:

0.00648

Gnomad ASJ exome

AF:

0.0121

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00359

Gnomad FIN exome

AF:

0.0612

Gnomad NFE exome

AF:

0.0232

Gnomad OTH exome

AF:

0.0181

GnomAD4 exome

AF:

0.0197

AC:

28795

AN:

1461712

Hom.:

385

Cov.:

AF XY:

0.0193

AC XY:

14055

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.00278

Gnomad4 AMR exome

AF:

0.00707

Gnomad4 ASJ exome

AF:

0.0122

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00380

Gnomad4 FIN exome

AF:

0.0592

Gnomad4 NFE exome

AF:

0.0212

Gnomad4 OTH exome

AF:

0.0164

GnomAD4 genome

AF:

0.0170

AC:

2584

AN:

152220

Hom.:

Cov.:

AF XY:

0.0186

AC XY:

1385

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00385

Gnomad4 AMR

AF:

0.0103

Gnomad4 ASJ

AF:

0.0112

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00352

Gnomad4 FIN

AF:

0.0615

Gnomad4 NFE

AF:

0.0223

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.0196

Hom.:

Bravo

AF:

0.0126

TwinsUK

AF:

0.0205

AC:

ALSPAC

AF:

0.0200

AC:

ESP6500AA

AF:

0.00454

AC:

ESP6500EA

AF:

0.0213

AC:

183

ExAC

AF:

0.0183

AC:

2223

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0189

EpiControl

AF:

0.0174

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.17

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.93

MetaRNN

Benign

0.0077

MetaSVM

Uncertain

0.17

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.44

Sift

Uncertain

0.018

Sift4G

Benign

0.11

Polyphen

1.0

Vest4

0.27

MPC

0.64

ClinPred

0.018

GERP RS

5.8

Varity_R

0.11

gMVP

0.60

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