dbSNP rs2240158: GRIN3B:p.Thr577Met (chr19-1005231-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_138690.3(GRIN3B):c.1730C>T(p.Thr577Met) variant causes a missense change. The variant allele was found at a frequency of 0.382 in 1,613,224 control chromosomes in the GnomAD database, including 120,816 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.40 ( 12967 hom., cov: 33)

Exomes 𝑓: 0.38 ( 107849 hom. )

Consequence

GRIN3B
NM_138690.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.14

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0050599575).

BP6

Variant 19-1005231-C-T is Benign according to our data. Variant chr19-1005231-C-T is described in ClinVar as [Benign]. Clinvar id is 1292493.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN3B	NM_138690.3 link	c.1730C>T	p.Thr577Met	missense_variant	Exon 3 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.1730C>T	p.Thr577Met	missense_variant	Exon 3 of 9	1	NM_138690.3	ENSP00000234389.3		O60391
GRIN3B	ENST00000588335.1 link	n.480C>T		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.405

AC:

61560

AN:

151988

Hom.:

12959

Cov.:

show subpopulations

Gnomad AFR

AF:

0.508

Gnomad AMI

AF:

0.201

Gnomad AMR

AF:

0.303

Gnomad ASJ

AF:

0.345

Gnomad EAS

AF:

0.168

Gnomad SAS

AF:

0.327

Gnomad FIN

AF:

0.434

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.391

Gnomad OTH

AF:

0.367

GnomAD3 exomes

AF:

0.365

AC:

91276

AN:

250132

Hom.:

17418

AF XY:

0.363

AC XY:

49222

AN XY:

135570

show subpopulations

Gnomad AFR exome

AF:

0.508

Gnomad AMR exome

AF:

0.314

Gnomad ASJ exome

AF:

0.354

Gnomad EAS exome

AF:

0.161

Gnomad SAS exome

AF:

0.333

Gnomad FIN exome

AF:

0.444

Gnomad NFE exome

AF:

0.389

Gnomad OTH exome

AF:

0.342

GnomAD4 exome

AF:

0.380

AC:

555390

AN:

1461118

Hom.:

107849

Cov.:

AF XY:

0.379

AC XY:

275239

AN XY:

726914

show subpopulations

Gnomad4 AFR exome

AF:

0.512

Gnomad4 AMR exome

AF:

0.309

Gnomad4 ASJ exome

AF:

0.355

Gnomad4 EAS exome

AF:

0.170

Gnomad4 SAS exome

AF:

0.335

Gnomad4 FIN exome

AF:

0.438

Gnomad4 NFE exome

AF:

0.389

Gnomad4 OTH exome

AF:

0.367

GnomAD4 genome

AF:

0.405

AC:

61601

AN:

152106

Hom.:

12967

Cov.:

AF XY:

0.402

AC XY:

29917

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.508

Gnomad4 AMR

AF:

0.303

Gnomad4 ASJ

AF:

0.345

Gnomad4 EAS

AF:

0.168

Gnomad4 SAS

AF:

0.328

Gnomad4 FIN

AF:

0.434

Gnomad4 NFE

AF:

0.391

Gnomad4 OTH

AF:

0.365

Alfa

AF:

0.388

Hom.:

22968

Bravo

AF:

0.400

TwinsUK

AF:

0.391

AC:

1449

ALSPAC

AF:

0.395

AC:

1521

ESP6500AA

AF:

0.506

AC:

2228

ESP6500EA

AF:

0.387

AC:

3324

ExAC

AF:

0.369

AC:

44740

Asia WGS

AF:

0.272

AC:

949

AN:

3478

EpiCase

AF:

0.380

EpiControl

AF:

0.383

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 21, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 24814139) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.11

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0051

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.9

PrimateAI

Uncertain

0.64

PROVEAN

Benign

3.8

REVEL

Benign

0.095

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.036

Vest4

0.073

MPC

0.12

ClinPred

0.0056

GERP RS

4.5

Varity_R

0.068

gMVP

0.75

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