NM_133445.3:c.2615-2194G>A

Variant names:

• chr9-101615721-C-T
• rs10121600
• NM_133445.3:c.2615-2194G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133445.3(GRIN3A):​c.2615-2194G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 151,974 control chromosomes in the GnomAD database, including 12,164 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 0.39 (12164 hom., cov: 31)
• Consequence: GRIN3A NM_133445.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN3A	NM_133445.3	c.2615-2194G>A		intron_variant	Intron 5 of 8	ENST00000361820.6	NP_597702.2
GRIN3A	XM_011518211.3	c.2615-2194G>A		intron_variant	Intron 5 of 6		XP_011516513.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN3A	ENST00000361820.6	c.2615-2194G>A		intron_variant	Intron 5 of 8	1	NM_133445.3	ENSP00000355155.3
ENSG00000299588	ENST00000764873.1	n.223+9346C>T		intron_variant	Intron 2 of 4
ENSG00000299588	ENST00000764875.1	n.198+9346C>T		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59063 AN: 151856 Hom.: 12121 Cov.: 31

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.380

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.389 AC: 59164 AN: 151974 Hom.: 12164 Cov.: 31 AF XY: 0.386 AC XY: 28635 AN XY: 74258

African (AFR) AF: 0.524 AC: 21716 AN: 41446

American (AMR) AF: 0.351 AC: 5369 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1231 AN: 3468

East Asian (EAS) AF: 0.240 AC: 1234 AN: 5146

South Asian (SAS) AF: 0.306 AC: 1476 AN: 4820

European-Finnish (FIN) AF: 0.368 AC: 3874 AN: 10536

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22961 AN: 67960

Other (OTH) AF: 0.381 AC: 803 AN: 2110

Alfa AF: 0.354 Hom.: 24973

Bravo AF: 0.390

Asia WGS AF: 0.357 AC: 1243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.69
PhyloP100		-0.073
Mutation Taster		=100/0	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: rs10121600; hg19: chr9-104378003;