5-178986946-T-C

Variant names:

Variant summary

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

The NM_000843.4(GRM6):c.1392A>G(p.Gly464Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 1,613,232 control chromosomes in the GnomAD database, including 319,953 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 25577 hom., cov: 33)

Exomes 𝑓: 0.63 ( 294376 hom. )

Consequence

GRM6
NM_000843.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: -0.891

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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 5-178986946-T-C is Benign according to our data. Variant chr5-178986946-T-C is described in ClinVar as [Benign]. Clinvar id is 99628.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-178986946-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.891 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM6	NM_000843.4 link	c.1392A>G	p.Gly464Gly	synonymous_variant	Exon 8 of 11	ENST00000517717.3	NP_000834.2	O15303
ZNF454	XR_007058600.1 link	n.5644-2801T>C		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM6	ENST00000517717.3 link	c.1392A>G	p.Gly464Gly	synonymous_variant	Exon 8 of 11	5	NM_000843.4	ENSP00000430767.1		O15303

Frequencies

GnomAD3 genomes

AF:

0.572

AC:

86838

AN:

151892

Hom.:

25551

Cov.:

show subpopulations

Gnomad AFR

AF:

0.435

Gnomad AMI

AF:

0.470

Gnomad AMR

AF:

0.600

Gnomad ASJ

AF:

0.609

Gnomad EAS

AF:

0.569

Gnomad SAS

AF:

0.504

Gnomad FIN

AF:

0.615

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.647

Gnomad OTH

AF:

0.553

GnomAD3 exomes

AF:

0.600

AC:

149877

AN:

249822

Hom.:

45705

AF XY:

0.596

AC XY:

80555

AN XY:

135168

show subpopulations

Gnomad AFR exome

AF:

0.431

Gnomad AMR exome

AF:

0.620

Gnomad ASJ exome

AF:

0.608

Gnomad EAS exome

AF:

0.582

Gnomad SAS exome

AF:

0.493

Gnomad FIN exome

AF:

0.621

Gnomad NFE exome

AF:

0.645

Gnomad OTH exome

AF:

0.606

GnomAD4 exome

AF:

0.632

AC:

923228

AN:

1461220

Hom.:

294376

Cov.:

AF XY:

0.627

AC XY:

455474

AN XY:

726890

show subpopulations

Gnomad4 AFR exome

AF:

0.427

Gnomad4 AMR exome

AF:

0.619

Gnomad4 ASJ exome

AF:

0.606

Gnomad4 EAS exome

AF:

0.557

Gnomad4 SAS exome

AF:

0.492

Gnomad4 FIN exome

AF:

0.625

Gnomad4 NFE exome

AF:

0.655

Gnomad4 OTH exome

AF:

0.612

GnomAD4 genome

AF:

0.572

AC:

86910

AN:

152012

Hom.:

25577

Cov.:

AF XY:

0.569

AC XY:

42266

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.436

Gnomad4 AMR

AF:

0.601

Gnomad4 ASJ

AF:

0.609

Gnomad4 EAS

AF:

0.568

Gnomad4 SAS

AF:

0.506

Gnomad4 FIN

AF:

0.615

Gnomad4 NFE

AF:

0.647

Gnomad4 OTH

AF:

0.558

Alfa

AF:

0.623

Hom.:

50574

Bravo

AF:

0.568

Asia WGS

AF:

0.572

AC:

1989

AN:

3478

EpiCase

AF:

0.624

EpiControl

AF:

0.619

ClinVar

Significance: Benign

Submissions summary: Benign:4Other: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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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:1

Mar 19, 2015

Eurofins Ntd Llc (ga)

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

-0.66

CADD

Benign

DANN

Benign

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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