Genetic Variant GRM5:p.Ser1167Phe (chr11-88508731-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001143831.3(GRM5):c.3500C>T(p.Ser1167Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GRM5
NM_001143831.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.48

Publications

0 publications found

Variant links:

Genes affected

GRM5 (HGNC:4597): (glutamate metabotropic receptor 5) This gene encodes a member of the G-protein coupled receptor 3 protein family. The encoded protein is a metabatropic glutamate receptor, whose signaling activates a phosphatidylinositol-calcium second messenger system. This protein may be involved in the regulation of neural network activity and synaptic plasticity. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. A pseudogene of this gene has been defined on chromosome 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

GRM5 links:

GRM5-AS1 (HGNC:40265): (GRM5 antisense RNA 1)

GRM5-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143831.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GRM5	NM_001143831.3	MANE Select	c.3500C>T	p.Ser1167Phe	missense	Exon 10 of 10	NP_001137303.1	P41594-1
GRM5	NM_000842.5		c.3404C>T	p.Ser1135Phe	missense	Exon 9 of 9	NP_000833.1	P41594-2
GRM5	NM_001384268.1		c.3404C>T	p.Ser1135Phe	missense	Exon 9 of 9	NP_001371197.1	P41594-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GRM5	ENST00000305447.5	TSL:1 MANE Select	c.3500C>T	p.Ser1167Phe	missense	Exon 10 of 10	ENSP00000306138.4	P41594-1
GRM5	ENST00000305432.9	TSL:1	c.3404C>T	p.Ser1135Phe	missense	Exon 8 of 8	ENSP00000305905.5	P41594-2
GRM5	ENST00000962224.1		c.3500C>T	p.Ser1167Phe	missense	Exon 10 of 10	ENSP00000632283.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1433024

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

712768

African (AFR)

AF:

0.00

AC:

AN:

30514

American (AMR)

AF:

0.00

AC:

AN:

41874

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24866

East Asian (EAS)

AF:

0.00

AC:

AN:

35814

South Asian (SAS)

AF:

0.00

AC:

AN:

84068

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51804

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5658

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1099402

Other (OTH)

AF:

0.00

AC:

AN:

59024

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.40

BayesDel_noAF

Pathogenic

0.34

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

M_CAP

Pathogenic

0.59

MetaRNN

Uncertain

0.61

MetaSVM

Pathogenic

1.0

MutationAssessor

Benign

1.9

PhyloP100

9.5

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-3.0

REVEL

Pathogenic

0.80

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.46

MutPred

0.48

Gain of catalytic residue at S1167 (P = 0.0018)

MVP

0.80

ClinPred

1.0

GERP RS

4.9

Varity_R

0.85

gMVP

0.79

Mutation Taster

=36/64

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over