Variant rs1455514264 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001143831.3(GRM5):c.3247G>T(p.Ala1083Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,429,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GRM5
NM_001143831.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.230

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.073152125).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM5	NM_001143831.3 link	c.3247G>T	p.Ala1083Ser	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.3247G>T	p.Ala1083Ser	missense_variant	Exon 10 of 10	1	NM_001143831.3	ENSP00000306138.4	P41594-1
GRM5	ENST00000305432.9 link	c.3151G>T	p.Ala1051Ser	missense_variant	Exon 8 of 8	1		ENSP00000305905.5	P41594-2
GRM5	ENST00000455756.6 link	c.3151G>T	p.Ala1051Ser	missense_variant	Exon 9 of 9	2		ENSP00000405690.2	P41594-2
GRM5-AS1	ENST00000526448.1 link	n.4364+45C>A		intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000525

AC:

AN:

190440

Hom.:

AF XY:

0.00000978

AC XY:

AN XY:

102246

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000124

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1429556

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

707782

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000183

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

2.8

DANN

Benign

0.88

DEOGEN2

Benign

0.10

.;.;T

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.71

T;.;T

M_CAP

Pathogenic

0.63

MetaRNN

Benign

0.073

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

-0.12

.;.;N

PrimateAI

Uncertain

0.65

PROVEAN

Benign

0.070

N;N;N

REVEL

Benign

0.13

Sift

Benign

0.69

T;T;T

Sift4G

Benign

0.79

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.048

MutPred

0.14

.;.;Gain of glycosylation at A1083 (P = 0.0332);

MVP

0.31

ClinPred

0.071

GERP RS

-0.92

Varity_R

0.082

gMVP

0.28

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over