5-178981601-T-G

Position:

• chr5-178981601-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000843.4(GRM6):​c.*56A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0402 in 1,395,726 control chromosomes in the GnomAD database, including 1,719 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.036 (174 hom., cov: 32)
  • Exomes 𝑓: 0.041 (1545 hom.)
• Consequence: GRM6 NM_000843.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.37

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• 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	c.*56A>C		3_prime_UTR_variant	11/11	ENST00000517717.3
ZNF454	XR_007058600.1	n.5644-8146T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRM6	ENST00000517717.3	c.*56A>C		3_prime_UTR_variant	11/11	5	NM_000843.4	P1
	ENST00000519491.1	n.305-8146T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0356 AC: 5404 AN: 151998 Hom.: 173 Cov.: 32

Gnomad AFR AF: 0.00676

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0573

Gnomad ASJ AF: 0.0620

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.0849

Gnomad FIN AF: 0.0406

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0340

Gnomad OTH AF: 0.0451

GnomAD4 exome AF: 0.0408 AC: 50703 AN: 1243608 Hom.: 1545 Cov.: 18 AF XY: 0.0430 AC XY: 26952 AN XY: 627324

Gnomad4 AFR exome AF: 0.00690

Gnomad4 AMR exome AF: 0.0421

Gnomad4 ASJ exome AF: 0.0545

Gnomad4 EAS exome AF: 0.158

Gnomad4 SAS exome AF: 0.0910

Gnomad4 FIN exome AF: 0.0370

Gnomad4 NFE exome AF: 0.0321

Gnomad4 OTH exome AF: 0.0429

GnomAD4 genome AF: 0.0355 AC: 5404 AN: 152118 Hom.: 174 Cov.: 32 AF XY: 0.0377 AC XY: 2801 AN XY: 74342

Gnomad4 AFR AF: 0.00672

Gnomad4 AMR AF: 0.0573

Gnomad4 ASJ AF: 0.0620

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.0847

Gnomad4 FIN AF: 0.0406

Gnomad4 NFE AF: 0.0340

Gnomad4 OTH AF: 0.0455

Alfa AF: 0.0348 Hom.: 96

Bravo AF: 0.0333

Asia WGS AF: 0.0940 AC: 324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs17078853; hg19: chr5-178408602;