NM_001143831.3:c.3246C>A

Variant names:

• chr11-88508985-G-T
• rs1290464463
• NM_001143831.3:c.3246C>A

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.3246C>A​(p.Thr1082Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,429,662 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. T1082T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GRM5 NM_001143831.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810
• 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=-0.59).
• BP7: Synonymous conserved (PhyloP=-0.081 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.3246C>A	p.Thr1082Thr	synonymous	Exon 10 of 10	NP_001137303.1	P41594-1
	GRM5	NM_000842.5		c.3150C>A	p.Thr1050Thr	synonymous	Exon 9 of 9	NP_000833.1	P41594-2
	GRM5	NM_001384268.1		c.3150C>A	p.Thr1050Thr	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.3246C>A	p.Thr1082Thr	synonymous	Exon 10 of 10	ENSP00000306138.4	P41594-1
	GRM5	ENST00000305432.9	TSL:1	c.3150C>A	p.Thr1050Thr	synonymous	Exon 8 of 8	ENSP00000305905.5	P41594-2
	GRM5	ENST00000962224.1		c.3246C>A	p.Thr1082Thr	synonymous	Exon 10 of 10	ENSP00000632283.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000524 AC: 1 AN: 190860 AF XY: 0.00000976

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: 0.0000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1429662 Hom.: 0 Cov.: 34 AF XY: 0.00000283 AC XY: 2 AN XY: 707840

African (AFR) AF: 0.00 AC: 0 AN: 32852

American (AMR) AF: 0.00 AC: 0 AN: 39594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25424

East Asian (EAS) AF: 0.00 AC: 0 AN: 38446

South Asian (SAS) AF: 0.00 AC: 0 AN: 81624

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51026

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1095736

Other (OTH) AF: 0.00 AC: 0 AN: 59242

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000508 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	6.4
DANN	Benign	0.88
PhyloP100		-0.081

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: rs1290464463; hg19: chr11-88242153;