11-88508754-C-T

Variant names:

• chr11-88508754-C-T
• rs745961968
• NM_001143831.3:c.3477G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001143831.3(GRM5):​c.3477G>A​(p.Glu1159Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,400,040 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: GRM5 NM_001143831.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.26
• 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=2.26 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM5	NM_001143831.3	c.3477G>A	p.Glu1159Glu	synonymous_variant	Exon 10 of 10	ENST00000305447.5	NP_001137303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM5	ENST00000305447.5	c.3477G>A	p.Glu1159Glu	synonymous_variant	Exon 10 of 10	1	NM_001143831.3	ENSP00000306138.4
GRM5	ENST00000305432.9	c.3381G>A	p.Glu1127Glu	synonymous_variant	Exon 8 of 8	1		ENSP00000305905.5
GRM5	ENST00000455756.6	c.3381G>A	p.Glu1127Glu	synonymous_variant	Exon 9 of 9	2		ENSP00000405690.2
GRM5-AS1	ENST00000526448.1	n.4179C>T		non_coding_transcript_exon_variant	Exon 1 of 6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1400040 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 694140

African (AFR) AF: 0.00 AC: 0 AN: 29316

American (AMR) AF: 0.00 AC: 0 AN: 36850

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23034

East Asian (EAS) AF: 0.00 AC: 0 AN: 33904

South Asian (SAS) AF: 0.00 AC: 0 AN: 78998

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50026

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5544

European-Non Finnish (NFE) AF: 9.22e-7 AC: 1 AN: 1084688

Other (OTH) AF: 0.00 AC: 0 AN: 57680

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Benign	0.95
PhyloP100		2.3

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: rs745961968; hg19: chr11-88241922;