rs2645339

Positions:

Variant summary

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

The NM_000843.4(GRM6):c.1227C>T(p.Tyr409=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 1,613,020 control chromosomes in the GnomAD database, including 237,047 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 19491 hom., cov: 33)

Exomes 𝑓: 0.54 ( 217556 hom. )

Consequence

GRM6
NM_000843.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: -0.947

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 5-178989062-G-A is Benign according to our data. Variant chr5-178989062-G-A is described in ClinVar as [Benign]. Clinvar id is 99626.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-178989062-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.947 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM6	NM_000843.4 linkuse as main transcript	c.1227C>T	p.Tyr409=	synonymous_variant	7/11	ENST00000517717.3	NP_000834.2
ZNF454	XR_007058600.1 linkuse as main transcript	n.5644-685G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
GRM6	ENST00000517717.3 linkuse as main transcript	c.1227C>T	p.Tyr409=	synonymous_variant	7/11	5	NM_000843.4	ENSP00000430767	P1
	ENST00000519491.1 linkuse as main transcript	n.305-685G>A		intron_variant, non_coding_transcript_variant		3
GRM6	ENST00000231188.9 linkuse as main transcript	c.1227C>T	p.Tyr409=	synonymous_variant	6/10	2		ENSP00000231188	P1
GRM6	ENST00000650031.1 linkuse as main transcript	c.1227C>T	p.Tyr409=	synonymous_variant	8/12			ENSP00000497110	P1

Frequencies

GnomAD3 genomes

AF:

0.500

AC:

75981

AN:

151878

Hom.:

19464

Cov.:

show subpopulations

Gnomad AFR

AF:

0.399

Gnomad AMI

AF:

0.311

Gnomad AMR

AF:

0.527

Gnomad ASJ

AF:

0.477

Gnomad EAS

AF:

0.565

Gnomad SAS

AF:

0.469

Gnomad FIN

AF:

0.560

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.548

Gnomad OTH

AF:

0.472

GnomAD3 exomes

AF:

0.528

AC:

131968

AN:

249712

Hom.:

35359

AF XY:

0.523

AC XY:

70667

AN XY:

135144

show subpopulations

Gnomad AFR exome

AF:

0.398

Gnomad AMR exome

AF:

0.571

Gnomad ASJ exome

AF:

0.475

Gnomad EAS exome

AF:

0.581

Gnomad SAS exome

AF:

0.453

Gnomad FIN exome

AF:

0.560

Gnomad NFE exome

AF:

0.545

Gnomad OTH exome

AF:

0.526

GnomAD4 exome

AF:

0.544

AC:

794400

AN:

1461024

Hom.:

217556

Cov.:

AF XY:

0.539

AC XY:

391933

AN XY:

726812

show subpopulations

Gnomad4 AFR exome

AF:

0.392

Gnomad4 AMR exome

AF:

0.568

Gnomad4 ASJ exome

AF:

0.474

Gnomad4 EAS exome

AF:

0.551

Gnomad4 SAS exome

AF:

0.452

Gnomad4 FIN exome

AF:

0.562

Gnomad4 NFE exome

AF:

0.556

Gnomad4 OTH exome

AF:

0.531

GnomAD4 genome

AF:

0.500

AC:

76047

AN:

151996

Hom.:

19491

Cov.:

AF XY:

0.502

AC XY:

37288

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.399

Gnomad4 AMR

AF:

0.528

Gnomad4 ASJ

AF:

0.477

Gnomad4 EAS

AF:

0.564

Gnomad4 SAS

AF:

0.471

Gnomad4 FIN

AF:

0.560

Gnomad4 NFE

AF:

0.548

Gnomad4 OTH

AF:

0.478

Alfa

AF:

0.524

Hom.:

10638

Bravo

AF:

0.496

Asia WGS

AF:

0.551

AC:

1915

AN:

3478

EpiCase

AF:

0.525

EpiControl

AF:

0.518

ClinVar

Significance: Benign

Submissions summary: Benign:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3Other:1

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Likely benign, no assertion criteria provided	literature only	Department of Ophthalmology and Visual Sciences Kyoto University	-	- -
not provided, no classification provided	literature only	Retina International	-	- -

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 10, 2014	- -

Congenital stationary night blindness 1B

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

3.5

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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