Genetic Variant NM_133445.3:c.1660T>C (chr9-101670752-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_133445.3(GRIN3A):c.1660T>C(p.Leu554Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,613,574 control chromosomes in the GnomAD database, including 122,987 homozygotes. 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 0.33 ( 9450 hom., cov: 33)

Exomes 𝑓: 0.39 ( 113537 hom. )

Consequence

GRIN3A
NM_133445.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.146

Publications

18 publications found

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:

ENSG00000299588 (HGNC:):

ENSG00000299588 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP7

Synonymous conserved (PhyloP=-0.146 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN3A	NM_133445.3 link	c.1660T>C	p.Leu554Leu	synonymous_variant	Exon 3 of 9	ENST00000361820.6	NP_597702.2	Q8TCU5
GRIN3A	XM_011518211.3 link	c.1660T>C	p.Leu554Leu	synonymous_variant	Exon 3 of 7		XP_011516513.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN3A	ENST00000361820.6 link	c.1660T>C	p.Leu554Leu	synonymous_variant	Exon 3 of 9	1	NM_133445.3	ENSP00000355155.3		Q8TCU5

Frequencies

GnomAD3 genomes

AF:

0.335

AC:

50898

AN:

152020

Hom.:

9445

Cov.:

show subpopulations

Gnomad AFR

AF:

0.178

Gnomad AMI

AF:

0.331

Gnomad AMR

AF:

0.394

Gnomad ASJ

AF:

0.435

Gnomad EAS

AF:

0.214

Gnomad SAS

AF:

0.301

Gnomad FIN

AF:

0.382

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.415

Gnomad OTH

AF:

0.364

GnomAD2 exomes

AF:

0.365

AC:

91639

AN:

251034

AF XY:

0.368

show subpopulations

Gnomad AFR exome

AF:

0.172

Gnomad AMR exome

AF:

0.379

Gnomad ASJ exome

AF:

0.422

Gnomad EAS exome

AF:

0.208

Gnomad FIN exome

AF:

0.391

Gnomad NFE exome

AF:

0.414

Gnomad OTH exome

AF:

0.397

GnomAD4 exome

AF:

0.390

AC:

569668

AN:

1461436

Hom.:

113537

Cov.:

AF XY:

0.389

AC XY:

282751

AN XY:

727034

show subpopulations

African (AFR)

AF:

0.169

AC:

5671

AN:

33460

American (AMR)

AF:

0.379

AC:

16918

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.417

AC:

10892

AN:

26128

East Asian (EAS)

AF:

0.189

AC:

7499

AN:

39696

South Asian (SAS)

AF:

0.319

AC:

27528

AN:

86252

European-Finnish (FIN)

AF:

0.388

AC:

20706

AN:

53412

Middle Eastern (MID)

AF:

0.393

AC:

2266

AN:

5766

European-Non Finnish (NFE)

AF:

0.409

AC:

455146

AN:

1111648

Other (OTH)

AF:

0.382

AC:

23042

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

22032

44064

66096

88128

110160

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.335

AC:

50922

AN:

152138

Hom.:

9450

Cov.:

AF XY:

0.332

AC XY:

24683

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.178

AC:

7394

AN:

41526

American (AMR)

AF:

0.394

AC:

6026

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.435

AC:

1508

AN:

3470

East Asian (EAS)

AF:

0.214

AC:

1102

AN:

5144

South Asian (SAS)

AF:

0.302

AC:

1458

AN:

4826

European-Finnish (FIN)

AF:

0.382

AC:

4042

AN:

10584

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.415

AC:

28218

AN:

67982

Other (OTH)

AF:

0.364

AC:

768

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1678

3356

5035

6713

8391

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.384

Hom.:

36274

Bravo

AF:

0.329

Asia WGS

AF:

0.308

AC:

1070

AN:

3478

EpiCase

AF:

0.406

EpiControl

AF:

0.408

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.25

(source)

DANN

Benign

0.48

PhyloP100

-0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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NM_133445.3:c.1660T>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over