Variant 19-1000567-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_138690.3(GRIN3B):c.130C>T(p.Pro44Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 1,058,698 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00097 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 5 hom. )

Consequence

GRIN3B
NM_138690.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.52

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3121369).

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN3B	NM_138690.3 linkuse as main transcript	c.130C>T	p.Pro44Ser	missense_variant	1/9	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.130C>T	p.Pro44Ser	missense_variant	1/9	1	NM_138690.3	ENSP00000234389	P1
	ENST00000588380.1 linkuse as main transcript	n.270-400G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000972

AC:

143

AN:

147130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00176

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000115

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00163

Gnomad OTH

AF:

0.000492

GnomAD4 exome

AF:

0.00177

AC:

1616

AN:

911460

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

751

AN XY:

427142

show subpopulations

Gnomad4 AFR exome

AF:

0.000285

Gnomad4 AMR exome

AF:

0.000302

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000389

Gnomad4 FIN exome

AF:

0.000247

Gnomad4 NFE exome

AF:

0.00189

Gnomad4 OTH exome

AF:

0.00207

GnomAD4 genome

AF:

0.000971

AC:

143

AN:

147238

Hom.:

Cov.:

AF XY:

0.000920

AC XY:

AN XY:

71726

show subpopulations

Gnomad4 AFR

AF:

0.000171

Gnomad4 AMR

AF:

0.00175

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000115

Gnomad4 NFE

AF:

0.00163

Gnomad4 OTH

AF:

0.000487

Alfa

AF:

0.00244

Hom.:

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

Oct 13, 2021

The c.130C>T (p.P44S) alteration is located in exon 1 (coding exon 1) of the GRIN3B gene. This alteration results from a C to T substitution at nucleotide position 130, causing the proline (P) at amino acid position 44 to be replaced by a serine (S). 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

0.51

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.051

Eigen

Benign

0.13

Eigen_PC

Benign

0.046

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.59

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

0.64

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.3

REVEL

Benign

0.096

Sift

Benign

0.28

Sift4G

Benign

0.062

Polyphen

1.0

Vest4

0.36

MVP

0.64

MPC

0.15

ClinPred

0.91

GERP RS

2.3

Varity_R

0.069

gMVP

0.80

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