chr19-1000786-C-A

Variant names:

• chr19-1000786-C-A
• NM_138690.3:c.349C>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.349C>A​(p.His117Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000772 in 1,294,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: GRIN3B NM_138690.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.997

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]

ENSG00000266990 (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=0.16349751).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN3B	NM_138690.3	c.349C>A	p.His117Asn	missense_variant	Exon 1 of 9	ENST00000234389.3	NP_619635.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN3B	ENST00000234389.3	c.349C>A	p.His117Asn	missense_variant	Exon 1 of 9	1	NM_138690.3	ENSP00000234389.3
ENSG00000266990	ENST00000588380.1	n.270-619G>T		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.72e-7 AC: 1 AN: 1294624 Hom.: 0 Cov.: 40 AF XY: 0.00 AC XY: 0 AN XY: 637968

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000143

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	22
DANN	Benign	0.93
DEOGEN2	Benign	0.055	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.70	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.067
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.056	T
Polyphen		0.072	B
Vest4		0.20
MutPred		0.43		Gain of catalytic residue at H117 (P = 0.0231);
MVP		0.29
MPC		0.15
ClinPred		0.22	T
GERP RS		2.5
Varity_R		0.16
gMVP		0.42

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: chr19-1000785;