rs16920487

Positions:

• chr9-101571102-A-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_133445.3(GRIN3A):​c.*2072T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0606 in 152,312 control chromosomes in the GnomAD database, including 369 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 0.061 (369 hom., cov: 32)
  • Exomes 𝑓: 0.029 (0 hom.)
• Consequence: GRIN3A NM_133445.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.246

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN3A	NM_133445.3	c.*2072T>A		3_prime_UTR_variant	9/9	ENST00000361820.6	NP_597702.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN3A	ENST00000361820.6	c.*2072T>A		3_prime_UTR_variant	9/9	1	NM_133445.3	ENSP00000355155.3

Frequencies

GnomAD3 genomes AF: 0.0606 AC: 9219 AN: 152056 Hom.: 368 Cov.: 32

Gnomad AFR AF: 0.0147

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.0960

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.0700

Gnomad SAS AF: 0.0913

Gnomad FIN AF: 0.0883

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0738

Gnomad OTH AF: 0.0541

GnomAD4 exome AF: 0.0290 AC: 4 AN: 138 Hom.: 0 Cov.: 0 AF XY: 0.0300 AC XY: 3 AN XY: 100

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.0300

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0606 AC: 9225 AN: 152174 Hom.: 369 Cov.: 32 AF XY: 0.0629 AC XY: 4677 AN XY: 74388

Gnomad4 AFR AF: 0.0147

Gnomad4 AMR AF: 0.0965

Gnomad4 ASJ AF: 0.0392

Gnomad4 EAS AF: 0.0696

Gnomad4 SAS AF: 0.0918

Gnomad4 FIN AF: 0.0883

Gnomad4 NFE AF: 0.0738

Gnomad4 OTH AF: 0.0535

Alfa AF: 0.0669 Hom.: 55

Bravo AF: 0.0589

Asia WGS AF: 0.0960 AC: 333 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	17
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.42		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.42		Position offset: 9

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs16920487; hg19: chr9-104333384;