GRIP2 p.Ser494Arg

Variant names:

• chr3-14514305-T-G
• NM_001080423.4:c.1480A>C
• GRIP2 p.Ser494Arg

Your query was ambiguous. Multiple possible variants found:

• chr3-14514305-T-G
• chr3-14514303-A-T
• chr3-14514303-A-C
• chr3-14514303-ACT-GCG
• chr3-14514303-ACT-TCG
• chr3-14514303-ACT-CCG

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001080423.4(GRIP2):​c.1480A>C​(p.Ser494Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GRIP2 NM_001080423.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.61
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.819

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080423.4. 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
	GRIP2	NM_001080423.4	MANE Select	c.1480A>C	p.Ser494Arg	missense	Exon 12 of 24	NP_001073892.3	Q9C0E4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIP2	ENST00000621039.5	TSL:1 MANE Select	c.1480A>C	p.Ser494Arg	missense	Exon 12 of 24	ENSP00000478352.1	Q9C0E4-1
	GRIP2	ENST00000619221.4	TSL:5	c.1771A>C	p.Ser591Arg	missense	Exon 13 of 25	ENSP00000480660.1	A0A087WX15
	GRIP2	ENST00000637182.1	TSL:5	c.1495A>C	p.Ser499Arg	missense	Exon 12 of 24	ENSP00000490949.1	A0A1B0GWJ3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.34
CADD	Pathogenic	26
DANN	Benign	0.92
DEOGEN2	Benign	0.15	T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
MetaRNN	Pathogenic	0.82	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		7.6
PrimateAI	Uncertain	0.68	T
Sift4G	Benign	0.14	T
Varity_R		0.30
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-14555813;