Variant chr19-1003179-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138690.3(GRIN3B):c.476T>C(p.Leu159Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000122 in 1,507,954 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00011 ( 1 hom. )

Consequence

GRIN3B
NM_138690.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.66

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14710277).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN3B	NM_138690.3 linkuse as main transcript	c.476T>C	p.Leu159Pro	missense_variant	2/9	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.476T>C	p.Leu159Pro	missense_variant	2/9	1	NM_138690.3	ENSP00000234389	P1

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000181

AC:

AN:

137826

Hom.:

AF XY:

0.000223

AC XY:

AN XY:

76390

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000350

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000850

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000802

Gnomad OTH exome

AF:

0.000321

GnomAD4 exome

AF:

0.000110

AC:

149

AN:

1355608

Hom.:

Cov.:

AF XY:

0.000131

AC XY:

AN XY:

665536

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.000199

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000975

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000461

Gnomad4 OTH exome

AF:

0.000126

GnomAD4 genome

AF:

0.000230

AC:

AN:

152346

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000131

Hom.:

Bravo

AF:

0.000178

ExAC

AF:

0.000210

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 17, 2024

The c.476T>C (p.L159P) alteration is located in exon 2 (coding exon 2) of the GRIN3B gene. This alteration results from a T to C substitution at nucleotide position 476, causing the leucine (L) at amino acid position 159 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.051

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.65

M_CAP

Benign

0.062

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.80

REVEL

Benign

0.23

Sift

Benign

0.10

Sift4G

Benign

0.27

Polyphen

0.99

Vest4

0.74

MVP

0.41

MPC

0.45

ClinPred

0.079

GERP RS

3.4

Varity_R

0.56

gMVP

0.82

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