Variant 19-1000472-C-A 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.35C>A(p.Ala12Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000381 in 1,208,698 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

GRIN3B
NM_138690.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.591

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:

ENSG00000266990 (HGNC:):

ENSG00000266990 links:

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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=0.24353588).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN3B	NM_138690.3 linkuse as main transcript	c.35C>A	p.Ala12Glu	missense_variant	1/9	ENST00000234389.3	NP_619635.1	O60391Q5F0I5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN3B	ENST00000234389.3 linkuse as main transcript	c.35C>A	p.Ala12Glu	missense_variant	1/9	1	NM_138690.3	ENSP00000234389.3		O60391
ENSG00000266990	ENST00000588380.1 linkuse as main transcript	n.270-305G>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000119

AC:

AN:

151580

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000411

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000265

AC:

AN:

1057118

Hom.:

Cov.:

AF XY:

0.0000160

AC XY:

AN XY:

498906

show subpopulations

Gnomad4 AFR exome

AF:

0.00118

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000221

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000119

AC:

AN:

151580

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

AN XY:

74054

show subpopulations

Gnomad4 AFR

AF:

0.000411

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000230

ExAC

AF:

0.0000212

AC:

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

Sep 26, 2024

The c.35C>A (p.A12E) alteration is located in exon 1 (coding exon 1) of the GRIN3B gene. This alteration results from a C to A substitution at nucleotide position 35, causing the alanine (A) at amino acid position 12 to be replaced by a glutamic acid (E). 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

0.37

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.066

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.44

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.24

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.2

REVEL

Benign

0.18

Sift

Uncertain

0.013

Sift4G

Benign

0.13

Polyphen

0.64

Vest4

0.44

MutPred

0.62

Gain of helix (P = 0.062);

MVP

0.52

MPC

0.21

ClinPred

0.81

GERP RS

-1.8

Varity_R

0.15

gMVP

0.59

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