5-178983150-C-T

Variant names:

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.2196G>A(p.Thr732Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,613,502 control chromosomes in the GnomAD database, including 26,373 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 2846 hom., cov: 33)

Exomes 𝑓: 0.17 ( 23527 hom. )

Consequence

GRM6
NM_000843.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: -5.84

Publications

14 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=-0.57).

BP6

Variant 5-178983150-C-T is Benign according to our data. Variant chr5-178983150-C-T is described in ClinVar as Benign. ClinVar VariationId is 99643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.84 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM6	NM_000843.4 link	c.2196G>A	p.Thr732Thr	synonymous_variant	Exon 10 of 11	ENST00000517717.3	NP_000834.2	O15303
ZNF454	XR_007058600.1 link	n.5644-6597C>T		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM6	ENST00000517717.3 link	c.2196G>A	p.Thr732Thr	synonymous_variant	Exon 10 of 11	5	NM_000843.4	ENSP00000430767.1		O15303

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28558

AN:

152022

Hom.:

2841

Cov.:

show subpopulations

Gnomad AFR

AF:

0.205

Gnomad AMI

AF:

0.111

Gnomad AMR

AF:

0.187

Gnomad ASJ

AF:

0.167

Gnomad EAS

AF:

0.379

Gnomad SAS

AF:

0.295

Gnomad FIN

AF:

0.178

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.158

Gnomad OTH

AF:

0.203

GnomAD2 exomes

AF:

0.202

AC:

50710

AN:

251112

AF XY:

0.205

show subpopulations

Gnomad AFR exome

AF:

0.202

Gnomad AMR exome

AF:

0.191

Gnomad ASJ exome

AF:

0.161

Gnomad EAS exome

AF:

0.375

Gnomad FIN exome

AF:

0.177

Gnomad NFE exome

AF:

0.165

Gnomad OTH exome

AF:

0.197

GnomAD4 exome

AF:

0.172

AC:

251063

AN:

1461362

Hom.:

23527

Cov.:

AF XY:

0.175

AC XY:

127512

AN XY:

726992

show subpopulations

African (AFR)

AF:

0.206

AC:

6887

AN:

33470

American (AMR)

AF:

0.189

AC:

8452

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.159

AC:

4167

AN:

26136

East Asian (EAS)

AF:

0.396

AC:

15704

AN:

39698

South Asian (SAS)

AF:

0.279

AC:

24054

AN:

86248

European-Finnish (FIN)

AF:

0.175

AC:

9316

AN:

53204

Middle Eastern (MID)

AF:

0.194

AC:

1119

AN:

5768

European-Non Finnish (NFE)

AF:

0.153

AC:

170480

AN:

1111738

Other (OTH)

AF:

0.180

AC:

10884

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

11913

23827

35740

47654

59567

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6222

12444

18666

24888

31110

<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:

0.188

AC:

28598

AN:

152140

Hom.:

2846

Cov.:

AF XY:

0.192

AC XY:

14252

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.205

AC:

8524

AN:

41504

American (AMR)

AF:

0.187

AC:

2860

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

581

AN:

3472

East Asian (EAS)

AF:

0.380

AC:

1956

AN:

5154

South Asian (SAS)

AF:

0.295

AC:

1421

AN:

4818

European-Finnish (FIN)

AF:

0.178

AC:

1892

AN:

10606

Middle Eastern (MID)

AF:

0.170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.158

AC:

10773

AN:

67980

Other (OTH)

AF:

0.208

AC:

440

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1215

2430

3646

4861

6076

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

318

636

954

1272

1590

<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:

0.168

Hom.:

3445

Bravo

AF:

0.188

Asia WGS

AF:

0.334

AC:

1158

AN:

3478

EpiCase

AF:

0.167

EpiControl

AF:

0.168

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

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

-0.57

CADD

Benign

0.043

(source)

DANN

Benign

0.88

PhyloP100

-5.8

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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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