19-1000682-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138690.3(GRIN3B):c.245G>A(p.Arg82His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000025 in 1,200,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000025 (0 hom.)
• Consequence: GRIN3B NM_138690.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.14

Genes affected

GRIN3B (HGNC:16768): (glutamate ionotropic receptor NMDA type subunit 3B) The protein encoded by this gene is a subunit of an N-methyl-D-aspartate (NMDA) receptor. The encoded protein is found primarily in motor neurons, where it forms a heterotetramer with GRIN1 to create an excitatory glycine receptor. Variations in this gene have been proposed to be linked to schizophrenia. [provided by RefSeq, Nov 2015]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24232814).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIN3B	NM_138690.3	c.245G>A	p.Arg82His	missense_variant	1/9	ENST00000234389.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIN3B	ENST00000234389.3	c.245G>A	p.Arg82His	missense_variant	1/9	1	NM_138690.3	P1
	ENST00000588380.1	n.270-515C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000250 AC: 3 AN: 1200252 Hom.: 0 Cov.: 33 AF XY: 0.00000340 AC XY: 2 AN XY: 587940

Gnomad4 AFR exome AF: 0.0000414

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000188

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000102

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2021

The c.245G>A (p.R82H) alteration is located in exon 1 (coding exon 1) of the GRIN3B gene. This alteration results from a G to A substitution at nucleotide position 245, causing the arginine (R) at amino acid position 82 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.026	T
Eigen	Benign	0.035
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	0.99	N
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.058
Sift	Benign	0.053	T
Sift4G	Benign	0.12	T
Polyphen		1.0	D
Vest4		0.13
MutPred		0.27		Loss of solvent accessibility (P = 0.0128);
MVP		0.43
MPC		0.51
ClinPred		0.71	D
GERP RS		2.5
Varity_R		0.11
gMVP		0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-1000681;