rs2240154

Variant names:

• chr19-1003173-C-A
• rs2240154
• NM_138690.3:c.470C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-1003173-C-A
• chr19-1003173-C-G
• chr19-1003173-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138690.3(GRIN3B):​c.470C>A​(p.Thr157Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GRIN3B NM_138690.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230
• Publications: 30 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25582653).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN3B	NM_138690.3	c.470C>A	p.Thr157Lys	missense_variant	Exon 2 of 9	ENST00000234389.3	NP_619635.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN3B	ENST00000234389.3	c.470C>A	p.Thr157Lys	missense_variant	Exon 2 of 9	1	NM_138690.3	ENSP00000234389.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1342538 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 657486

African (AFR) AF: 0.00 AC: 0 AN: 27458

American (AMR) AF: 0.00 AC: 0 AN: 27750

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19436

East Asian (EAS) AF: 0.00 AC: 0 AN: 34510

South Asian (SAS) AF: 0.00 AC: 0 AN: 68850

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47782

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4980

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1056638

Other (OTH) AF: 0.00 AC: 0 AN: 55134

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.058	T
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.23
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.13
Sift	Benign	0.28	T
Sift4G	Benign	0.093	T
Polyphen		0.99	D
Vest4		0.44
MutPred		0.41		Gain of ubiquitination at T157 (P = 0.0311);
MVP		0.38
MPC		0.45
ClinPred		0.76	D
GERP RS		3.4
Varity_R		0.11
gMVP		0.71
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2240154; hg19: chr19-1003172;