Genetic Variant NM_133445.3:c.1821A>C (chr9-101670591-T-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.1821A>C(p.Ala607Ala) 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 1,613,588 control chromosomes in the GnomAD database, including 122,953 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 ( 9433 hom., cov: 33)

Exomes 𝑓: 0.39 ( 113520 hom. )

Consequence

GRIN3A
NM_133445.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.359

Publications

17 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:

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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=-0.58).

BP7

Synonymous conserved (PhyloP=-0.359 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.1821A>C	p.Ala607Ala	synonymous_variant	Exon 3 of 9	ENST00000361820.6	NP_597702.2	Q8TCU5
GRIN3A	XM_011518211.3 link	c.1821A>C	p.Ala607Ala	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.1821A>C	p.Ala607Ala	synonymous_variant	Exon 3 of 9	1	NM_133445.3	ENSP00000355155.3		Q8TCU5

Frequencies

GnomAD3 genomes

AF:

0.335

AC:

50855

AN:

151964

Hom.:

9429

Cov.:

show subpopulations

Gnomad AFR

AF:

0.178

Gnomad AMI

AF:

0.330

Gnomad AMR

AF:

0.394

Gnomad ASJ

AF:

0.435

Gnomad EAS

AF:

0.213

Gnomad SAS

AF:

0.300

Gnomad FIN

AF:

0.381

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.415

Gnomad OTH

AF:

0.362

GnomAD2 exomes

AF:

0.365

AC:

91253

AN:

250146

AF XY:

0.367

show subpopulations

Gnomad AFR exome

AF:

0.172

Gnomad AMR exome

AF:

0.379

Gnomad ASJ exome

AF:

0.422

Gnomad EAS exome

AF:

0.209

Gnomad FIN exome

AF:

0.391

Gnomad NFE exome

AF:

0.414

Gnomad OTH exome

AF:

0.397

GnomAD4 exome

AF:

0.390

AC:

569671

AN:

1461508

Hom.:

113520

Cov.:

AF XY:

0.389

AC XY:

282754

AN XY:

727080

show subpopulations

African (AFR)

AF:

0.170

AC:

5677

AN:

33474

American (AMR)

AF:

0.379

AC:

16914

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.417

AC:

10893

AN:

26130

East Asian (EAS)

AF:

0.189

AC:

7502

AN:

39698

South Asian (SAS)

AF:

0.319

AC:

27484

AN:

86254

European-Finnish (FIN)

AF:

0.388

AC:

20670

AN:

53318

Middle Eastern (MID)

AF:

0.393

AC:

2267

AN:

5768

European-Non Finnish (NFE)

AF:

0.409

AC:

455229

AN:

1111802

Other (OTH)

AF:

0.382

AC:

23035

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

23012

46025

69037

92050

115062

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13726

27452

41178

54904

68630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.335

AC:

50877

AN:

152080

Hom.:

9433

Cov.:

AF XY:

0.331

AC XY:

24640

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.178

AC:

7401

AN:

41526

American (AMR)

AF:

0.394

AC:

6023

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.435

AC:

1508

AN:

3470

East Asian (EAS)

AF:

0.213

AC:

1096

AN:

5144

South Asian (SAS)

AF:

0.301

AC:

1448

AN:

4816

European-Finnish (FIN)

AF:

0.381

AC:

4030

AN:

10576

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.415

AC:

28202

AN:

67950

Other (OTH)

AF:

0.362

AC:

764

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1686

3372

5059

6745

8431

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

498

996

1494

1992

2490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.388

Hom.:

23186

Bravo

AF:

0.329

Asia WGS

AF:

0.305

AC:

1060

AN:

3478

EpiCase

AF:

0.407

EpiControl

AF:

0.408

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

7.6

(source)

DANN

Benign

0.65

PhyloP100

-0.36

Mutation Taster

=98/2

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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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