Variant 19-1004711-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_138690.3(GRIN3B):c.1210C>T(p.Arg404Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 1,602,780 control chromosomes in the GnomAD database, including 205,128 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict 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 0.45 ( 16115 hom., cov: 33)

Exomes 𝑓: 0.50 ( 189013 hom. )

Consequence

GRIN3B
NM_138690.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.942

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:

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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=1.2913346E-4).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.523 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.1210C>T	p.Arg404Trp	missense_variant	3/9	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.1210C>T	p.Arg404Trp	missense_variant	3/9	1	NM_138690.3	ENSP00000234389	P1
GRIN3B	ENST00000588335.1 linkuse as main transcript	n.51-91C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.453

AC:

68868

AN:

151916

Hom.:

16110

Cov.:

show subpopulations

Gnomad AFR

AF:

0.398

Gnomad AMI

AF:

0.406

Gnomad AMR

AF:

0.382

Gnomad ASJ

AF:

0.474

Gnomad EAS

AF:

0.0858

Gnomad SAS

AF:

0.437

Gnomad FIN

AF:

0.481

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.528

Gnomad OTH

AF:

0.443

GnomAD3 exomes

AF:

0.443

AC:

103970

AN:

234738

Hom.:

24562

AF XY:

0.452

AC XY:

57949

AN XY:

128146

show subpopulations

Gnomad AFR exome

AF:

0.389

Gnomad AMR exome

AF:

0.362

Gnomad ASJ exome

AF:

0.477

Gnomad EAS exome

AF:

0.0809

Gnomad SAS exome

AF:

0.454

Gnomad FIN exome

AF:

0.481

Gnomad NFE exome

AF:

0.525

Gnomad OTH exome

AF:

0.454

GnomAD4 exome

AF:

0.503

AC:

729752

AN:

1450746

Hom.:

189013

Cov.:

AF XY:

0.503

AC XY:

362252

AN XY:

720390

show subpopulations

Gnomad4 AFR exome

AF:

0.384

Gnomad4 AMR exome

AF:

0.361

Gnomad4 ASJ exome

AF:

0.475

Gnomad4 EAS exome

AF:

0.0874

Gnomad4 SAS exome

AF:

0.456

Gnomad4 FIN exome

AF:

0.486

Gnomad4 NFE exome

AF:

0.534

Gnomad4 OTH exome

AF:

0.474

GnomAD4 genome

AF:

0.453

AC:

68900

AN:

152034

Hom.:

16115

Cov.:

AF XY:

0.450

AC XY:

33404

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.398

Gnomad4 AMR

AF:

0.381

Gnomad4 ASJ

AF:

0.474

Gnomad4 EAS

AF:

0.0861

Gnomad4 SAS

AF:

0.440

Gnomad4 FIN

AF:

0.481

Gnomad4 NFE

AF:

0.528

Gnomad4 OTH

AF:

0.439

Alfa

AF:

0.503

Hom.:

6015

Bravo

AF:

0.442

TwinsUK

AF:

0.527

AC:

1955

ALSPAC

AF:

0.537

AC:

2071

ESP6500AA

AF:

0.398

AC:

1746

ESP6500EA

AF:

0.520

AC:

4461

ExAC

AF:

0.442

AC:

53352

Asia WGS

AF:

0.265

AC:

925

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

4.6

DANN

Benign

0.82

DEOGEN2

Benign

0.18

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.54

MetaRNN

Benign

0.00013

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.90

REVEL

Benign

0.013

Sift

Benign

0.060

Sift4G

Uncertain

0.010

Polyphen

0.033

Vest4

0.12

MPC

0.12

ClinPred

0.0091

GERP RS

-3.3

Varity_R

0.053

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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