chr9-101573337-T-C

Variant names:

• chr9-101573337-T-C
• rs71509734
• NM_133445.3:c.3185A>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.11
• Publications: 10 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]

ACMG classification

Our verdict: Benign. The variant received -16 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 VariationId is 713863.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

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.3185A>G	p.Asn1062Ser	missense	Exon 9 of 9	NP_597702.2	Q8TCU5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIN3A	ENST00000361820.6	TSL:1 MANE Select	c.3185A>G	p.Asn1062Ser	missense	Exon 9 of 9	ENSP00000355155.3	Q8TCU5

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

GnomAD2 exomes AF: 0.00704 AC: 1768 AN: 251100 AF XY: 0.00737

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 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

African (AFR) AF: 0.00152 AC: 51 AN: 33470

American (AMR) AF: 0.00367 AC: 164 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00241 AC: 63 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86258

European-Finnish (FIN) AF: 0.00578 AC: 309 AN: 53418

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.0129 AC: 14327 AN: 1111958

Other (OTH) AF: 0.00995 AC: 601 AN: 60388

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

African (AFR) AF: 0.00197 AC: 82 AN: 41536

American (AMR) AF: 0.00582 AC: 89 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00425 AC: 45 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0116 AC: 788 AN: 68008

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.00999 Hom.: 25

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		6.1
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
Mutation Taster		=76/24	polymorphism

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: rs71509734; hg19: chr9-104335619;