11-66283279-GTC-ATT

Variant names:

• chr11-66283279-GTC-ATT
• NM_182553.3:c.343_345delGTCinsATT
• CNIH2 p.Val115Ile

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_182553.3(CNIH2):​c.343_345delGTCinsATT​(p.Val115Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CNIH2 NM_182553.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.19
• Publications: 0 publications found

Genes affected

CNIH2 (HGNC:28744): (cornichon family AMPA receptor auxiliary protein 2) The protein encoded by this gene is an auxiliary subunit of the ionotropic glutamate receptor of the AMPA subtype. AMPA receptors mediate fast synaptic neurotransmission in the central nervous system. This protein has been reported to interact with the Type I AMPA receptor regulatory protein isoform gamma-8 to control assembly of hippocampal AMPA receptor complexes, thereby modulating receptor gating and pharmacology. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182553.3. 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
	CNIH2	NM_182553.3	MANE Select	c.343_345delGTCinsATT	p.Val115Ile	missense	N/A	NP_872359.1	Q6PI25
	CNIH2	NR_073078.2		n.651_653delGTCinsATT		non_coding_transcript_exon	Exon 5 of 6
	CNIH2	NR_073079.2		n.621_623delGTCinsATT		non_coding_transcript_exon	Exon 5 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNIH2	ENST00000311445.7	TSL:1 MANE Select	c.343_345delGTCinsATT	p.Val115Ile	missense	N/A	ENSP00000310003.6	Q6PI25
	CNIH2	ENST00000528852.5	TSL:1	c.343_345delGTCinsATT	p.Val115Ile	missense	N/A	ENSP00000432177.1	E9PS15
	CNIH2	ENST00000528063.5	TSL:1	n.*180_*182delGTCinsATT		non_coding_transcript_exon	Exon 5 of 6	ENSP00000435537.1	E9PJQ8

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.2

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-66050750;