Genetic Variant GRIN3B:p.Thr157Met (chr19-1003173-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_138690.3(GRIN3B):c.470C>T(p.Thr157Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,494,280 control chromosomes in the GnomAD database, including 21,279 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.

Frequency

Genomes: 𝑓 0.13 ( 1998 hom., cov: 34)

Exomes 𝑓: 0.16 ( 19281 hom. )

Consequence

GRIN3B
NM_138690.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.230

Publications

30 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001303792).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN3B	NM_138690.3 link	c.470C>T	p.Thr157Met	missense_variant	Exon 2 of 9	ENST00000234389.3	NP_619635.1	O60391Q5F0I5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN3B	ENST00000234389.3 link	c.470C>T	p.Thr157Met	missense_variant	Exon 2 of 9	1	NM_138690.3	ENSP00000234389.3		O60391

Frequencies

GnomAD3 genomes

AF:

0.134

AC:

20448

AN:

152124

Hom.:

2000

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0321

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.230

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.434

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.135

Gnomad MID

AF:

0.0350

Gnomad NFE

AF:

0.154

Gnomad OTH

AF:

0.125

GnomAD2 exomes

AF:

0.189

AC:

24052

AN:

127250

AF XY:

0.181

show subpopulations

Gnomad AFR exome

AF:

0.0242

Gnomad AMR exome

AF:

0.324

Gnomad ASJ exome

AF:

0.113

Gnomad EAS exome

AF:

0.456

Gnomad FIN exome

AF:

0.128

Gnomad NFE exome

AF:

0.146

Gnomad OTH exome

AF:

0.159

GnomAD4 exome

AF:

0.160

AC:

214664

AN:

1342036

Hom.:

19281

Cov.:

AF XY:

0.159

AC XY:

104691

AN XY:

657204

show subpopulations

African (AFR)

AF:

0.0212

AC:

582

AN:

27452

American (AMR)

AF:

0.305

AC:

8445

AN:

27660

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

2242

AN:

19428

East Asian (EAS)

AF:

0.419

AC:

14450

AN:

34470

South Asian (SAS)

AF:

0.168

AC:

11592

AN:

68804

European-Finnish (FIN)

AF:

0.135

AC:

6463

AN:

47768

Middle Eastern (MID)

AF:

0.0813

AC:

405

AN:

4980

European-Non Finnish (NFE)

AF:

0.153

AC:

161701

AN:

1056362

Other (OTH)

AF:

0.159

AC:

8784

AN:

55112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

9464

18928

28393

37857

47321

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6104

12208

18312

24416

30520

<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

AF:

0.134

AC:

20441

AN:

152244

Hom.:

1998

Cov.:

AF XY:

0.137

AC XY:

10188

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0320

AC:

1330

AN:

41578

American (AMR)

AF:

0.231

AC:

3531

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.112

AC:

390

AN:

3472

East Asian (EAS)

AF:

0.433

AC:

2232

AN:

5158

South Asian (SAS)

AF:

0.163

AC:

786

AN:

4828

European-Finnish (FIN)

AF:

0.135

AC:

1427

AN:

10608

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.154

AC:

10452

AN:

67986

Other (OTH)

AF:

0.123

AC:

259

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

886

1773

2659

3546

4432

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

228

456

684

912

1140

<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:

0.151

Hom.:

3564

Bravo

AF:

0.139

TwinsUK

AF:

0.159

AC:

591

ALSPAC

AF:

0.148

AC:

572

ESP6500AA

AF:

0.0284

AC:

120

ESP6500EA

AF:

0.138

AC:

1154

ExAC

AF:

0.164

AC:

19336

Asia WGS

AF:

0.270

AC:

935

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.091

Eigen

Uncertain

0.29

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.69

MetaRNN

Benign

0.0013

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.2

PhyloP100

0.23

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.6

REVEL

Benign

0.049

Sift

Benign

0.093

Sift4G

Uncertain

0.018

Polyphen

1.0

Vest4

0.16

MPC

0.24

ClinPred

0.014

GERP RS

3.4

Varity_R

0.050

gMVP

0.53

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over