9-101670591-T-G

Variant names:

• chr9-101670591-T-G
• rs942142
• NM_133445.3:c.1821A>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359
• Publications: 17 publications found

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]

ENSG00000299588 (HGNC:):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133445.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIN3A	NM_133445.3	MANE Select	c.1821A>C	p.Ala607Ala	synonymous	Exon 3 of 9	NP_597702.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIN3A	ENST00000361820.6	TSL:1 MANE Select	c.1821A>C	p.Ala607Ala	synonymous	Exon 3 of 9	ENSP00000355155.3
	ENSG00000299588	ENST00000764873.1		n.224-54157T>G		intron	N/A
	ENSG00000299588	ENST00000764874.1		n.57+20038T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50855 AN: 151964 Hom.: 9429 Cov.: 33

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

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.: 46 AF XY: 0.389 AC XY: 282754 AN XY: 727080

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

GnomAD4 genome AF: 0.335 AC: 50877 AN: 152080 Hom.: 9433 Cov.: 33 AF XY: 0.331 AC XY: 24640 AN XY: 74332

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	7.6
DANN	Benign	0.65
PhyloP100		-0.36
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs942142; hg19: chr9-104432873; COSMIC: COSV62450864;