Genetic Variant GRM5:p.Glu1122Lys (chr11-88508867-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_001143831.3(GRM5):c.3364G>A(p.Glu1122Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000208 in 1,583,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

GRM5
NM_001143831.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.48

Publications

1 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: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.30085415).

BS2

High AC in GnomAd4 at 15 AD gene.

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.3364G>A	p.Glu1122Lys	missense	Exon 10 of 10	NP_001137303.1	P41594-1
GRM5	NM_000842.5		c.3268G>A	p.Glu1090Lys	missense	Exon 9 of 9	NP_000833.1	P41594-2
GRM5	NM_001384268.1		c.3268G>A	p.Glu1090Lys	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.3364G>A	p.Glu1122Lys	missense	Exon 10 of 10	ENSP00000306138.4	P41594-1
GRM5	ENST00000305432.9	TSL:1	c.3268G>A	p.Glu1090Lys	missense	Exon 8 of 8	ENSP00000305905.5	P41594-2
GRM5	ENST00000962224.1		c.3364G>A	p.Glu1122Lys	missense	Exon 10 of 10	ENSP00000632283.1

Frequencies

GnomAD3 genomes

AF:

0.0000987

AC:

AN:

151980

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:

0.000206

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000400

AC:

AN:

200184

AF XY:

0.0000365

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000794

Gnomad OTH exome

AF:

0.000203

GnomAD4 exome

AF:

0.000219

AC:

314

AN:

1431788

Hom.:

Cov.:

AF XY:

0.000206

AC XY:

146

AN XY:

710286

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31472

American (AMR)

AF:

0.00

AC:

AN:

40658

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25294

East Asian (EAS)

AF:

0.00

AC:

AN:

37452

South Asian (SAS)

AF:

0.00

AC:

AN:

81824

European-Finnish (FIN)

AF:

0.0000194

AC:

AN:

51480

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

0.000278

AC:

305

AN:

1098606

Other (OTH)

AF:

0.000135

AC:

AN:

59280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000987

AC:

AN:

151980

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74226

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41422

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5144

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

67954

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.545

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000767

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000249

AC:

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

Benign

0.32

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

Eigen

Benign

0.13

Eigen_PC

Benign

0.17

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.92

M_CAP

Pathogenic

0.67

MetaRNN

Benign

0.30

MetaSVM

Uncertain

-0.041

MutationAssessor

Uncertain

2.0

PhyloP100

6.5

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.37

Sift

Benign

0.085

Sift4G

Uncertain

0.015

Polyphen

0.93

Vest4

0.26

MVP

0.63

ClinPred

0.25

GERP RS

4.9

Varity_R

0.18

gMVP

0.59

Mutation Taster

=73/27

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over