3-6773301-C-G

Variant names:

• chr3-6773301-C-G
• ENST00000448328.6:c.-180+3183C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000448328.6(GRM7):​c.-180+3183C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000791 in 1,263,744 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: 31)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: GRM7 ENST00000448328.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.631

Genes affected

GRM7 (HGNC:4599): (glutamate metabotropic receptor 7) L-glutamate is the major excitatory neurotransmitter in the central nervous system, and it 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 three 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. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]

MRPS36P1 (HGNC:29771): (mitochondrial ribosomal protein S36 pseudogene 1)

GRM7-AS3 (HGNC:42444): (GRM7 antisense RNA 3)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPS36P1		n.6773301C>G		intragenic_variant
GRM7-AS3	NR_110123.1	n.150+17752G>C		intron_variant	Intron 2 of 3
GRM7-AS3	NR_110125.1	n.150+17752G>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM7	ENST00000448328.6	c.-180+3183C>G		intron_variant	Intron 1 of 4	4		ENSP00000393799.2
MRPS36P1	ENST00000421291.1	n.43G>C		non_coding_transcript_exon_variant	Exon 1 of 1	6
GRM7-AS3	ENST00000412629.6	n.180+17752G>C		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.91e-7 AC: 1 AN: 1263744 Hom.: 0 Cov.: 23 AF XY: 0.00000157 AC XY: 1 AN XY: 638382

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000107

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	11
DANN	Benign	0.60

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-6814988;