11-88508795-C-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_001143831.3(GRM5):c.3436G>T(p.Ala1146Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000174 in 1,467,490 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00097 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000083 ( 0 hom. )

Consequence

GRM5
NM_001143831.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.346

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 Benign. Variant got -9 ACMG points.

PP2

Missense variant where missense usually causes diseases, GRM5

BP4

Computational evidence support a benign effect (MetaRNN=0.0064635873).

BP6

Variant 11-88508795-C-A is Benign according to our data. Variant chr11-88508795-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 734163.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 144 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRM5	NM_001143831.3 linkuse as main transcript	c.3436G>T	p.Ala1146Ser	missense_variant	10/10	ENST00000305447.5
GRM5-AS1	NR_049724.1 linkuse as main transcript	n.4220C>A		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRM5	ENST00000305447.5 linkuse as main transcript	c.3436G>T	p.Ala1146Ser	missense_variant	10/10	1	NM_001143831.3	A2	P41594-1
GRM5	ENST00000305432.9 linkuse as main transcript	c.3340G>T	p.Ala1114Ser	missense_variant	8/8	1		P2	P41594-2
GRM5-AS1	ENST00000526448.1 linkuse as main transcript	n.4220C>A		non_coding_transcript_exon_variant	1/6	5
GRM5	ENST00000455756.6 linkuse as main transcript	c.3340G>T	p.Ala1114Ser	missense_variant	9/9	2		P2	P41594-2

Frequencies

GnomAD3 genomes

AF:

0.000948

AC:

144

AN:

151922

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00326

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000962

GnomAD3 exomes

AF:

0.000145

AC:

AN:

62106

Hom.:

AF XY:

0.000114

AC XY:

AN XY:

34972

show subpopulations

Gnomad AFR exome

AF:

0.00719

Gnomad AMR exome

AF:

0.000230

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000829

AC:

109

AN:

1315462

Hom.:

Cov.:

AF XY:

0.0000665

AC XY:

AN XY:

646480

show subpopulations

Gnomad4 AFR exome

AF:

0.00322

Gnomad4 AMR exome

AF:

0.000147

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:

0.00000191

Gnomad4 OTH exome

AF:

0.000350

GnomAD4 genome

AF:

0.000967

AC:

147

AN:

152028

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.00332

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.000951

Alfa

AF:

0.000712

Hom.:

Bravo

AF:

0.00100

ExAC

AF:

0.000175

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.38

Cadd

Benign

4.4

Dann

Benign

0.76

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.61

T;.;T

M_CAP

Pathogenic

0.47

MetaRNN

Benign

0.0065

T;T;T

MetaSVM

Benign

-0.83

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Uncertain

0.75

PROVEAN

Benign

0.080

N;N;N

REVEL

Benign

0.12

Sift

Benign

0.41

T;T;T

Sift4G

Benign

0.69

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.083

MVP

0.40

ClinPred

0.0087

GERP RS

2.3

Varity_R

0.039

gMVP

0.33

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over