Variant 5-178981834-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_000843.4(GRM6):c.2457G>A(p.Thr819=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00725 in 1,612,124 control chromosomes in the GnomAD database, including 634 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 73 hom., cov: 32)

Exomes 𝑓: 0.0069 ( 561 hom. )

Consequence

GRM6
NM_000843.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.39

Variant links:

Genes affected

GRM6 (HGNC:4598): (glutamate metabotropic receptor 6) 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. Mutations in this gene result in congenital stationary night blindness type 1B. [provided by RefSeq, May 2018]

GRM6 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 5-178981834-C-T is Benign according to our data. Variant chr5-178981834-C-T is described in ClinVar as [Benign]. Clinvar id is 1166033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRM6	NM_000843.4 linkuse as main transcript	c.2457G>A	p.Thr819=	synonymous_variant	11/11	ENST00000517717.3
ZNF454	XR_007058600.1 linkuse as main transcript	n.5644-7913C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRM6	ENST00000517717.3 linkuse as main transcript	c.2457G>A	p.Thr819=	synonymous_variant	11/11	5	NM_000843.4	P1
	ENST00000519491.1 linkuse as main transcript	n.305-7913C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0101

AC:

1535

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0317

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.144

Gnomad SAS

AF:

0.0110

Gnomad FIN

AF:

0.0115

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000706

Gnomad OTH

AF:

0.00956

GnomAD3 exomes

AF:

0.0172

AC:

4302

AN:

249850

Hom.:

200

AF XY:

0.0160

AC XY:

2160

AN XY:

135172

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.0267

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.143

Gnomad SAS exome

AF:

0.0111

Gnomad FIN exome

AF:

0.00856

Gnomad NFE exome

AF:

0.00104

Gnomad OTH exome

AF:

0.0109

GnomAD4 exome

AF:

0.00695

AC:

10143

AN:

1459824

Hom.:

561

Cov.:

AF XY:

0.00702

AC XY:

5102

AN XY:

726412

show subpopulations

Gnomad4 AFR exome

AF:

0.00126

Gnomad4 AMR exome

AF:

0.0277

Gnomad4 ASJ exome

AF:

0.00153

Gnomad4 EAS exome

AF:

0.157

Gnomad4 SAS exome

AF:

0.0112

Gnomad4 FIN exome

AF:

0.00802

Gnomad4 NFE exome

AF:

0.000490

Gnomad4 OTH exome

AF:

0.0104

GnomAD4 genome

AF:

0.0101

AC:

1537

AN:

152300

Hom.:

Cov.:

AF XY:

0.0119

AC XY:

889

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.0317

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.144

Gnomad4 SAS

AF:

0.0110

Gnomad4 FIN

AF:

0.0115

Gnomad4 NFE

AF:

0.000706

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00346

Hom.:

Bravo

AF:

0.0113

Asia WGS

AF:

0.0650

AC:

224

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000415

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	clinical testing	GeneDx	May 06, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

1.0

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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