Variant 7-86765277-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000840.3(GRM3):c.132G>A(p.Leu44=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00473 in 1,613,730 control chromosomes in the GnomAD database, including 270 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 147 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 123 hom. )

Consequence

GRM3
NM_000840.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.421

Variant links:

Genes affected

GRM3 (HGNC:4595): (glutamate metabotropic receptor 3) L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3 while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. [provided by RefSeq, Jul 2008]

GRM3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 7-86765277-G-A is Benign according to our data. Variant chr7-86765277-G-A is described in ClinVar as [Benign]. Clinvar id is 768176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.421 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GRM3	NM_000840.3 linkuse as main transcript	c.132G>A	p.Leu44=	synonymous_variant	2/6	ENST00000361669.7
GRM3	NM_001363522.2 linkuse as main transcript	c.132G>A	p.Leu44=	synonymous_variant	2/5
GRM3	XM_047420268.1 linkuse as main transcript	c.132G>A	p.Leu44=	synonymous_variant	3/7
GRM3	XM_017012073.3 linkuse as main transcript	c.132G>A	p.Leu44=	synonymous_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRM3	ENST00000361669.7 linkuse as main transcript	c.132G>A	p.Leu44=	synonymous_variant	2/6	1	NM_000840.3	P1	Q14832-1

Frequencies

GnomAD3 genomes

AF:

0.0239

AC:

3629

AN:

152074

Hom.:

147

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0808

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0102

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.000809

Gnomad OTH

AF:

0.0249

GnomAD3 exomes

AF:

0.00641

AC:

1605

AN:

250532

Hom.:

AF XY:

0.00461

AC XY:

624

AN XY:

135394

show subpopulations

Gnomad AFR exome

AF:

0.0807

Gnomad AMR exome

AF:

0.00482

Gnomad ASJ exome

AF:

0.00288

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000619

Gnomad OTH exome

AF:

0.00442

GnomAD4 exome

AF:

0.00274

AC:

4000

AN:

1461538

Hom.:

123

Cov.:

AF XY:

0.00242

AC XY:

1756

AN XY:

727078

show subpopulations

Gnomad4 AFR exome

AF:

0.0792

Gnomad4 AMR exome

AF:

0.00571

Gnomad4 ASJ exome

AF:

0.00256

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.000502

Gnomad4 OTH exome

AF:

0.00702

GnomAD4 genome

AF:

0.0239

AC:

3641

AN:

152192

Hom.:

147

Cov.:

AF XY:

0.0234

AC XY:

1739

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0809

Gnomad4 AMR

AF:

0.0102

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000809

Gnomad4 OTH

AF:

0.0246

Alfa

AF:

0.0105

Hom.:

Bravo

AF:

0.0281

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.000983

EpiControl

AF:

0.000771

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

4.2

DANN

Benign

0.74

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