11-88508975-T-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001143831.3(GRM5):c.3256A>C(p.Ser1086Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000252 in 1,585,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GRM5
NM_001143831.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.564

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.13573596).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM5	NM_001143831.3 link	c.3256A>C	p.Ser1086Arg	missense_variant	Exon 10 of 10	ENST00000305447.5	NP_001137303.1	P41594-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GRM5	ENST00000305447.5 link	c.3256A>C	p.Ser1086Arg	missense_variant	Exon 10 of 10	1	NM_001143831.3	ENSP00000306138.4	P41594-1
GRM5	ENST00000305432.9 link	c.3160A>C	p.Ser1054Arg	missense_variant	Exon 8 of 8	1		ENSP00000305905.5	P41594-2
GRM5	ENST00000455756.6 link	c.3160A>C	p.Ser1054Arg	missense_variant	Exon 9 of 9	2		ENSP00000405690.2	P41594-2
GRM5-AS1	ENST00000526448.1 link	n.4364+36T>G		intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000102

AC:

AN:

196668

AF XY:

0.00000944

show subpopulations

Gnomad AFR exome

AF:

0.000181

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1433656

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

710194

show subpopulations

African (AFR)

AF:

0.0000304

AC:

AN:

32920

American (AMR)

AF:

0.00

AC:

AN:

40218

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25492

East Asian (EAS)

AF:

0.00

AC:

AN:

38630

South Asian (SAS)

AF:

0.00

AC:

AN:

82048

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51290

Middle Eastern (MID)

AF:

0.000175

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1097978

Other (OTH)

AF:

0.00

AC:

AN:

59356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152086

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41446

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67984

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 22, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.3256A>C (p.S1086R) alteration is located in exon 9 (coding exon 9) of the GRM5 gene. This alteration results from a A to C substitution at nucleotide position 3256, causing the serine (S) at amino acid position 1086 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

.;.;T

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.66

T;.;T

M_CAP

Pathogenic

0.80

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-0.65

MutationAssessor

Benign

0.90

.;.;L

PhyloP100

0.56

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.16

Sift

Benign

0.045

D;D;D

Sift4G

Benign

0.33

T;T;D

Polyphen

0.34

B;B;B

Vest4

0.13

MutPred

0.33

.;.;Loss of glycosylation at S1086 (P = 0.0207);

MVP

0.26

ClinPred

0.073

GERP RS

3.8

Varity_R

0.12

gMVP

0.61

Mutation Taster

=90/10

polymorphism

(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.

11-88508975-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over