7-111122873-CG-AA

Variant names:

• chr7-111122873-CG-AA
• NM_001099658.2:c.101_102delCGinsAA
• LRRN3 p.Thr34Lys

Variant summary

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

The NM_001099658.2(LRRN3):​c.101_102delCGinsAA​(p.Thr34Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 32)
• Consequence: LRRN3 NM_001099658.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.41
• Publications: 0 publications found

Genes affected

LRRN3 (HGNC:17200): (leucine rich repeat neuronal 3) Predicted to act upstream of or within positive regulation of synapse assembly. Predicted to be integral component of membrane. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

IMMP2L (HGNC:14598): (inner mitochondrial membrane peptidase subunit 2) This gene encodes a protein involved in processing the signal peptide sequences used to direct mitochondrial proteins to the mitochondria. The encoded protein resides in the mitochondria and is one of the necessary proteins for the catalytic activity of the mitochondrial inner membrane peptidase (IMP) complex. Two variants that encode the same protein have been described for this gene. [provided by RefSeq, Sep 2011]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099658.2. 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
	LRRN3	NM_001099658.2	MANE Select	c.101_102delCGinsAA	p.Thr34Lys	missense	N/A	NP_001093128.1	Q9H3W5
	IMMP2L	NM_032549.4	MANE Select	c.240-159309_240-159308delCGinsTT		intron	N/A	NP_115938.1	Q96T52-1
	LRRN3	NM_001099660.2		c.101_102delCGinsAA	p.Thr34Lys	missense	N/A	NP_001093130.1	A4D0T1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRN3	ENST00000308478.10	TSL:1 MANE Select	c.101_102delCGinsAA	p.Thr34Lys	missense	N/A	ENSP00000312001.5	Q9H3W5
	LRRN3	ENST00000422987.3	TSL:1	c.101_102delCGinsAA	p.Thr34Lys	missense	N/A	ENSP00000412417.2	Q9H3W5
	IMMP2L	ENST00000405709.7	TSL:1 MANE Select	c.240-159309_240-159308delCGinsTT		intron	N/A	ENSP00000384966.2	Q96T52-1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.4

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: chr7-110762929;