Variant rs12986002 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_138690.3(GRIN3B):c.349C>T(p.His117Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 1,435,580 control chromosomes in the GnomAD database, including 151,015 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 12864 hom., cov: 30)

Exomes 𝑓: 0.46 ( 138151 hom. )

Consequence

GRIN3B
NM_138690.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.997

Variant links:

Genes affected

GRIN3B (HGNC:16768): (glutamate ionotropic receptor NMDA type subunit 3B) The protein encoded by this gene is a subunit of an N-methyl-D-aspartate (NMDA) receptor. The encoded protein is found primarily in motor neurons, where it forms a heterotetramer with GRIN1 to create an excitatory glycine receptor. Variations in this gene have been proposed to be linked to schizophrenia. [provided by RefSeq, Nov 2015]

GRIN3B links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.9942393E-4).

BP6

Variant 19-1000786-C-T is Benign according to our data. Variant chr19-1000786-C-T is described in ClinVar as [Benign]. Clinvar id is 1274762.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN3B	NM_138690.3 linkuse as main transcript	c.349C>T	p.His117Tyr	missense_variant	1/9	ENST00000234389.3	NP_619635.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN3B	ENST00000234389.3 linkuse as main transcript	c.349C>T	p.His117Tyr	missense_variant	1/9	1	NM_138690.3	ENSP00000234389	P1
	ENST00000588380.1 linkuse as main transcript	n.270-619G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.429

AC:

60701

AN:

141380

Hom.:

12872

Cov.:

show subpopulations

Gnomad AFR

AF:

0.321

Gnomad AMI

AF:

0.658

Gnomad AMR

AF:

0.439

Gnomad ASJ

AF:

0.411

Gnomad EAS

AF:

0.289

Gnomad SAS

AF:

0.294

Gnomad FIN

AF:

0.479

Gnomad MID

AF:

0.378

Gnomad NFE

AF:

0.498

Gnomad OTH

AF:

0.421

GnomAD3 exomes

AF:

0.419

AC:

24713

AN:

59028

Hom.:

5462

AF XY:

0.405

AC XY:

14374

AN XY:

35488

show subpopulations

Gnomad AFR exome

AF:

0.300

Gnomad AMR exome

AF:

0.443

Gnomad ASJ exome

AF:

0.400

Gnomad EAS exome

AF:

0.313

Gnomad SAS exome

AF:

0.290

Gnomad FIN exome

AF:

0.481

Gnomad NFE exome

AF:

0.494

Gnomad OTH exome

AF:

0.424

GnomAD4 exome

AF:

0.457

AC:

591176

AN:

1294090

Hom.:

138151

Cov.:

AF XY:

0.452

AC XY:

288290

AN XY:

637648

show subpopulations

Gnomad4 AFR exome

AF:

0.279

Gnomad4 AMR exome

AF:

0.427

Gnomad4 ASJ exome

AF:

0.396

Gnomad4 EAS exome

AF:

0.251

Gnomad4 SAS exome

AF:

0.285

Gnomad4 FIN exome

AF:

0.481

Gnomad4 NFE exome

AF:

0.482

Gnomad4 OTH exome

AF:

0.425

GnomAD4 genome

AF:

0.429

AC:

60697

AN:

141490

Hom.:

12864

Cov.:

AF XY:

0.425

AC XY:

29376

AN XY:

69128

show subpopulations

Gnomad4 AFR

AF:

0.320

Gnomad4 AMR

AF:

0.438

Gnomad4 ASJ

AF:

0.411

Gnomad4 EAS

AF:

0.289

Gnomad4 SAS

AF:

0.293

Gnomad4 FIN

AF:

0.479

Gnomad4 NFE

AF:

0.498

Gnomad4 OTH

AF:

0.418

Alfa

AF:

0.433

Hom.:

1826

Bravo

AF:

0.395

ExAC

AF:

0.210

AC:

4833

Asia WGS

AF:

0.261

AC:

897

AN:

3430

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 25, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.069

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.67

MetaRNN

Benign

0.00030

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-1.1

REVEL

Benign

0.096

Sift

Uncertain

0.023

Sift4G

Uncertain

0.015

Polyphen

0.54

Vest4

0.069

MPC

0.13

ClinPred

0.0031

GERP RS

2.5

Varity_R

0.12

gMVP

0.47

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