rs4613440

Positions:

• chr3-14514303-A-C
• chr3-14514303-A-G

Variant summary

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

The NM_001080423.4(GRIP2):​c.1482T>G​(p.Ser494Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 29)
• Consequence: GRIP2 NM_001080423.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.01

Genes affected

GRIP2 (HGNC:23841): (glutamate receptor interacting protein 2) Predicted to enable protein C-terminus binding activity. Predicted to be involved in several processes, including neurotransmitter receptor transport, endosome to postsynaptic membrane; positive regulation of AMPA glutamate receptor clustering; and positive regulation of excitatory postsynaptic potential. Predicted to act upstream of or within Notch signaling pathway; artery smooth muscle contraction; and positive regulation of blood pressure. Predicted to be located in cytoplasm; dendritic shaft; and neuron spine. Predicted to be active in glutamatergic synapse and postsynaptic density. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIP2	NM_001080423.4	c.1482T>G	p.Ser494Arg	missense_variant	12/24	ENST00000621039.5	NP_001073892.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIP2	ENST00000621039.5	c.1482T>G	p.Ser494Arg	missense_variant	12/24	1	NM_001080423.4	ENSP00000478352.1
GRIP2	ENST00000619221.4	c.1773T>G	p.Ser591Arg	missense_variant	13/25	5		ENSP00000480660.1
GRIP2	ENST00000637182.1	c.1497T>G	p.Ser499Arg	missense_variant	12/24	5		ENSP00000490949.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 47

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.27
CADD	Uncertain	24
DANN	Benign	0.84
DEOGEN2	Benign	0.15	T;.;.
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.97	D;D;D
MetaRNN	Uncertain	0.64	D;D;D
MutationAssessor	Uncertain	2.8	M;.;.
PrimateAI	Uncertain	0.68	T
Sift4G	Benign	0.14	T;T;.
Polyphen		0.99	D;.;.
Vest4		0.85
MVP		0.72
GERP RS		2.9
Varity_R		0.079
gMVP		0.90

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: rs4613440; hg19: chr3-14555811;