11-88508877-C-A

Variant names:

• chr11-88508877-C-A
• rs767608328
• NM_001143831.3:c.3354G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001143831.3(GRM5):​c.3354G>T​(p.Leu1118Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,437,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L1118L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: GRM5 NM_001143831.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.190
• Publications: 0 publications found

Genes affected

GRM5 (HGNC:4597): (glutamate metabotropic receptor 5) This gene encodes a member of the G-protein coupled receptor 3 protein family. The encoded protein is a metabatropic glutamate receptor, whose signaling activates a phosphatidylinositol-calcium second messenger system. This protein may be involved in the regulation of neural network activity and synaptic plasticity. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. A pseudogene of this gene has been defined on chromosome 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

GRM5-AS1 (HGNC:40265): (GRM5 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=0.19 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143831.3. 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
	GRM5	NM_001143831.3	MANE Select	c.3354G>T	p.Leu1118Leu	synonymous	Exon 10 of 10	NP_001137303.1	P41594-1
	GRM5	NM_000842.5		c.3258G>T	p.Leu1086Leu	synonymous	Exon 9 of 9	NP_000833.1	P41594-2
	GRM5	NM_001384268.1		c.3258G>T	p.Leu1086Leu	synonymous	Exon 9 of 9	NP_001371197.1	P41594-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM5	ENST00000305447.5	TSL:1 MANE Select	c.3354G>T	p.Leu1118Leu	synonymous	Exon 10 of 10	ENSP00000306138.4	P41594-1
	GRM5	ENST00000305432.9	TSL:1	c.3258G>T	p.Leu1086Leu	synonymous	Exon 8 of 8	ENSP00000305905.5	P41594-2
	GRM5	ENST00000962224.1		c.3354G>T	p.Leu1118Leu	synonymous	Exon 10 of 10	ENSP00000632283.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000477 AC: 1 AN: 209806 AF XY: 0.00000873

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1437974 Hom.: 0 Cov.: 34 AF XY: 0.00000140 AC XY: 1 AN XY: 713696

African (AFR) AF: 0.00 AC: 0 AN: 31806

American (AMR) AF: 0.00 AC: 0 AN: 41662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25474

East Asian (EAS) AF: 0.00 AC: 0 AN: 37926

South Asian (SAS) AF: 0.0000121 AC: 1 AN: 82434

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51786

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101628

Other (OTH) AF: 0.00 AC: 0 AN: 59536

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	16
DANN	Benign	0.93
PhyloP100		0.19

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: rs767608328; hg19: chr11-88242045;