Variant chr9-101573437-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_133445.3(GRIN3A):c.3085T>C(p.Phe1029Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00387 in 1,614,028 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 19 hom. )

Consequence

GRIN3A
NM_133445.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.50

Variant links:

Genes affected

GRIN3A (HGNC:16767): (glutamate ionotropic receptor NMDA type subunit 3A) This gene encodes a subunit of the N-methyl-D-aspartate (NMDA) receptors, which belong to the superfamily of glutamate-regulated ion channels, and function in physiological and pathological processes in the central nervous system. This subunit shows greater than 90% identity to the corresponding subunit in rat. Studies in the knockout mouse deficient in this subunit suggest that this gene may be involved in the development of synaptic elements by modulating NMDA receptor activity. [provided by RefSeq, Jul 2008]

GRIN3A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003691256).

BP6

Variant 9-101573437-A-G is Benign according to our data. Variant chr9-101573437-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 773510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIN3A	NM_133445.3 linkuse as main transcript	c.3085T>C	p.Phe1029Leu	missense_variant	9/9	ENST00000361820.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN3A	ENST00000361820.6 linkuse as main transcript	c.3085T>C	p.Phe1029Leu	missense_variant	9/9	1	NM_133445.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00220

AC:

335

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000942

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00378

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00214

AC:

538

AN:

250980

Hom.:

AF XY:

0.00217

AC XY:

294

AN XY:

135638

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00199

Gnomad NFE exome

AF:

0.00371

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00404

AC:

5904

AN:

1461794

Hom.:

Cov.:

AF XY:

0.00384

AC XY:

2792

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.00145

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00178

Gnomad4 NFE exome

AF:

0.00497

Gnomad4 OTH exome

AF:

0.00328

GnomAD4 genome

AF:

0.00220

AC:

335

AN:

152234

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

131

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.000939

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.00378

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00283

Hom.:

Bravo

AF:

0.00221

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00701

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00360

AC:

ExAC

AF:

0.00220

AC:

267

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00382

EpiControl

AF:

0.00367

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.051

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.61

M_CAP

Benign

0.0027

MetaRNN

Benign

0.0037

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

MutationTaster

Benign

0.92

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.47

REVEL

Benign

0.099

Sift

Benign

0.25

Sift4G

Benign

0.67

Polyphen

0.0

Vest4

0.031

MutPred

0.26

Loss of catalytic residue at F1029 (P = 0.0772);

MVP

0.39

MPC

0.15

ClinPred

0.015

GERP RS

4.4

Varity_R

0.13

gMVP

0.24

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