5-178981601-T-G

Variant names:

• chr5-178981601-T-G
• rs17078853
• NM_000843.4:c.*56A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

ENSG00000254035 (HGNC:):

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000843.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM6	NM_000843.4	MANE Select	c.*56A>C		3_prime_UTR	Exon 11 of 11	NP_000834.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM6	ENST00000517717.3	TSL:5 MANE Select	c.*56A>C		3_prime_UTR	Exon 11 of 11	ENSP00000430767.1
	GRM6	ENST00000650488.1		n.1413A>C		non_coding_transcript_exon	Exon 2 of 2
	GRM6	ENST00000231188.9	TSL:2	c.*56A>C		3_prime_UTR	Exon 10 of 10	ENSP00000231188.5

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

African (AFR) AF: 0.00690 AC: 202 AN: 29278

American (AMR) AF: 0.0421 AC: 1840 AN: 43704

Ashkenazi Jewish (ASJ) AF: 0.0545 AC: 1316 AN: 24148

East Asian (EAS) AF: 0.158 AC: 6102 AN: 38528

South Asian (SAS) AF: 0.0910 AC: 7313 AN: 80374

European-Finnish (FIN) AF: 0.0370 AC: 1950 AN: 52732

Middle Eastern (MID) AF: 0.0568 AC: 279 AN: 4910

European-Non Finnish (NFE) AF: 0.0321 AC: 29430 AN: 916936

Other (OTH) AF: 0.0429 AC: 2271 AN: 52998

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

African (AFR) AF: 0.00672 AC: 279 AN: 41534

American (AMR) AF: 0.0573 AC: 876 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0620 AC: 215 AN: 3466

East Asian (EAS) AF: 0.144 AC: 738 AN: 5130

South Asian (SAS) AF: 0.0847 AC: 407 AN: 4804

European-Finnish (FIN) AF: 0.0406 AC: 430 AN: 10598

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0340 AC: 2312 AN: 67982

Other (OTH) AF: 0.0455 AC: 96 AN: 2108

Alfa AF: 0.0340 Hom.: 126

Bravo AF: 0.0333

Asia WGS AF: 0.0940 AC: 324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.48
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17078853; hg19: chr5-178408602;