9-101573337-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_133445.3(GRIN3A):c.3185A>G(p.Asn1062Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0103 in 1,614,028 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0068 (5 hom., cov: 32)
  • Exomes 𝑓: 0.011 (101 hom.)
• Consequence: GRIN3A NM_133445.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.11

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008609295).
• BP6: Variant 9-101573337-T-C is Benign according to our data. Variant chr9-101573337-T-C is described in ClinVar as [Benign]. Clinvar id is 713863.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIN3A	NM_133445.3	c.3185A>G	p.Asn1062Ser	missense_variant	9/9	ENST00000361820.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN3A	ENST00000361820.6	c.3185A>G	p.Asn1062Ser	missense_variant	9/9	1	NM_133445.3	P1

Frequencies

GnomAD3 genomes AF: 0.00682 AC: 1037 AN: 152102 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00198

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.00583

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00425

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0116

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00704 AC: 1768 AN: 251100 Hom.: 12 AF XY: 0.00737 AC XY: 1000 AN XY: 135704

Gnomad AFR exome AF: 0.00160

Gnomad AMR exome AF: 0.00373

Gnomad ASJ exome AF: 0.00189

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00587

Gnomad NFE exome AF: 0.0126

Gnomad OTH exome AF: 0.00653

GnomAD4 exome AF: 0.0106 AC: 15533 AN: 1461808 Hom.: 101 Cov.: 31 AF XY: 0.0105 AC XY: 7605 AN XY: 727206

Gnomad4 AFR exome AF: 0.00152

Gnomad4 AMR exome AF: 0.00367

Gnomad4 ASJ exome AF: 0.00241

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00578

Gnomad4 NFE exome AF: 0.0129

Gnomad4 OTH exome AF: 0.00995

GnomAD4 genome AF: 0.00681 AC: 1037 AN: 152220 Hom.: 5 Cov.: 32 AF XY: 0.00609 AC XY: 453 AN XY: 74418

Gnomad4 AFR AF: 0.00197

Gnomad4 AMR AF: 0.00582

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00425

Gnomad4 NFE AF: 0.0116

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.0100 Hom.: 20

Bravo AF: 0.00673

TwinsUK AF: 0.0102 AC: 38

ALSPAC AF: 0.0104 AC: 40

ESP6500AA AF: 0.00250 AC: 11

ESP6500EA AF: 0.0101 AC: 87

ExAC AF: 0.00764 AC: 927

Asia WGS AF: 0.000867 AC: 3 AN: 3476

EpiCase AF: 0.00982

EpiControl AF: 0.0107

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.59
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.085	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D
MetaRNN	Benign	0.0086	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.13
Sift	Uncertain	0.024	D
Sift4G	Benign	0.20	T
Polyphen		1.0	D
Vest4		0.52
MVP		0.71
MPC		0.52
ClinPred		0.014	T
GERP RS		5.5
Varity_R		0.12
gMVP		0.33

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

LitVar

Other links and lift over

dbSNP: rs71509734; hg19: chr9-104335619;