rs2645339

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000843.4(GRM6):c.1227C>T(p.Tyr409Tyr) 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

Publications

22 publications found

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:

ENSG00000254035 (HGNC:):

ENSG00000254035 links:

ZNF454 (HGNC:21200): (zinc finger protein 454) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF454 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 99626.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
GRM6	NM_000843.4 link	c.1227C>T	p.Tyr409Tyr	synonymous_variant	Exon 7 of 11	ENST00000517717.3	NP_000834.2
ZNF454	XR_007058600.1 link	n.5644-685G>A		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM6	ENST00000517717.3 link	c.1227C>T	p.Tyr409Tyr	synonymous_variant	Exon 7 of 11	5	NM_000843.4	ENSP00000430767.1

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

GnomAD2 exomes

AF:

0.528

AC:

131968

AN:

249712

AF XY:

0.523

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 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

African (AFR)

AF:

0.392

AC:

13129

AN:

33460

American (AMR)

AF:

0.568

AC:

25375

AN:

44662

Ashkenazi Jewish (ASJ)

AF:

0.474

AC:

12385

AN:

26128

East Asian (EAS)

AF:

0.551

AC:

21856

AN:

39672

South Asian (SAS)

AF:

0.452

AC:

38959

AN:

86214

European-Finnish (FIN)

AF:

0.562

AC:

29986

AN:

53362

Middle Eastern (MID)

AF:

0.423

AC:

2440

AN:

5764

European-Non Finnish (NFE)

AF:

0.556

AC:

618246

AN:

1111402

Other (OTH)

AF:

0.531

AC:

32024

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

22782

45564

68347

91129

113911

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17398

34796

52194

69592

86990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.500

AC:

76047

AN:

151996

Hom.:

19491

Cov.:

AF XY:

0.502

AC XY:

37288

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.399

AC:

16541

AN:

41444

American (AMR)

AF:

0.528

AC:

8076

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.477

AC:

1651

AN:

3464

East Asian (EAS)

AF:

0.564

AC:

2887

AN:

5120

South Asian (SAS)

AF:

0.471

AC:

2272

AN:

4826

European-Finnish (FIN)

AF:

0.560

AC:

5931

AN:

10584

Middle Eastern (MID)

AF:

0.452

AC:

133

AN:

294

European-Non Finnish (NFE)

AF:

0.548

AC:

37266

AN:

67956

Other (OTH)

AF:

0.478

AC:

1008

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1936

3873

5809

7746

9682

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

678

1356

2034

2712

3390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.523

Hom.:

10700

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

Department of Ophthalmology and Visual Sciences Kyoto University

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Retina International

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

not specified

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 10, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Congenital stationary night blindness 1B

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

3.5

(source)

DANN

Benign

0.89

PhyloP100

-0.95

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over