5-178981529-C-T

Variant names:

• chr5-178981529-C-T
• rs114396608
• NM_000843.4:c.*128G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000843.4(GRM6):​c.*128G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0324 in 705,758 control chromosomes in the GnomAD database, including 543 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.026 (80 hom., cov: 32)
  • Exomes 𝑓: 0.034 (463 hom.)
• Consequence: GRM6 NM_000843.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.839
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-178981529-C-T is Benign according to our data. Variant chr5-178981529-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1707172.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0671 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM6	NM_000843.4	MANE Select	c.*128G>A		3_prime_UTR	Exon 11 of 11	NP_000834.2	O15303

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM6	ENST00000517717.3	TSL:5 MANE Select	c.*128G>A		3_prime_UTR	Exon 11 of 11	ENSP00000430767.1	O15303
	GRM6	ENST00000231188.9	TSL:2	c.*128G>A		3_prime_UTR	Exon 10 of 10	ENSP00000231188.5	O15303
	GRM6	ENST00000650031.1		c.*128G>A		3_prime_UTR	Exon 12 of 12	ENSP00000497110.1	O15303

Frequencies

GnomAD3 genomes AF: 0.0256 AC: 3885 AN: 152022 Hom.: 79 Cov.: 32

Gnomad AFR AF: 0.00546

Gnomad AMI AF: 0.0374

Gnomad AMR AF: 0.0257

Gnomad ASJ AF: 0.0602

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0736

Gnomad FIN AF: 0.0291

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0333

Gnomad OTH AF: 0.0354

GnomAD4 exome AF: 0.0343 AC: 18988 AN: 553618 Hom.: 463 Cov.: 7 AF XY: 0.0376 AC XY: 10888 AN XY: 289618

African (AFR) AF: 0.00693 AC: 103 AN: 14870

American (AMR) AF: 0.0171 AC: 402 AN: 23486

Ashkenazi Jewish (ASJ) AF: 0.0555 AC: 831 AN: 14968

East Asian (EAS) AF: 0.000188 AC: 6 AN: 31894

South Asian (SAS) AF: 0.0808 AC: 4037 AN: 49978

European-Finnish (FIN) AF: 0.0287 AC: 1197 AN: 41700

Middle Eastern (MID) AF: 0.0519 AC: 113 AN: 2176

European-Non Finnish (NFE) AF: 0.0329 AC: 11349 AN: 345176

Other (OTH) AF: 0.0323 AC: 950 AN: 29370

GnomAD4 genome AF: 0.0255 AC: 3883 AN: 152140 Hom.: 80 Cov.: 32 AF XY: 0.0259 AC XY: 1927 AN XY: 74380

African (AFR) AF: 0.00542 AC: 225 AN: 41532

American (AMR) AF: 0.0256 AC: 392 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0602 AC: 209 AN: 3470

East Asian (EAS) AF: 0.00117 AC: 6 AN: 5150

South Asian (SAS) AF: 0.0734 AC: 353 AN: 4806

European-Finnish (FIN) AF: 0.0291 AC: 308 AN: 10582

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

European-Non Finnish (NFE) AF: 0.0333 AC: 2265 AN: 67998

Other (OTH) AF: 0.0351 AC: 74 AN: 2110

Alfa AF: 0.0311 Hom.: 24

Bravo AF: 0.0221

Asia WGS AF: 0.0290 AC: 99 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.57
PhyloP100		-0.84
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs114396608; hg19: chr5-178408530;