7-111122785-C-T

Variant names:

• chr7-111122785-C-T
• rs139409404
• NM_001099658.2:c.13C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001099658.2(LRRN3):​c.13C>T​(p.Pro5Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P5T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LRRN3 NM_001099658.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.49
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.121860266).

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.13C>T	p.Pro5Ser	missense	Exon 3 of 3	NP_001093128.1	Q9H3W5
	IMMP2L	NM_032549.4	MANE Select	c.240-159220G>A		intron	N/A	NP_115938.1	Q96T52-1
	LRRN3	NM_001099660.2		c.13C>T	p.Pro5Ser	missense	Exon 4 of 4	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.13C>T	p.Pro5Ser	missense	Exon 3 of 3	ENSP00000312001.5	Q9H3W5
	LRRN3	ENST00000422987.3	TSL:1	c.13C>T	p.Pro5Ser	missense	Exon 2 of 2	ENSP00000412417.2	Q9H3W5
	IMMP2L	ENST00000405709.7	TSL:1 MANE Select	c.240-159220G>A		intron	N/A	ENSP00000384966.2	Q96T52-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459562 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 725926

African (AFR) AF: 0.00 AC: 0 AN: 33432

American (AMR) AF: 0.00 AC: 0 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25920

East Asian (EAS) AF: 0.00 AC: 0 AN: 39646

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85876

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110786

Other (OTH) AF: 0.00 AC: 0 AN: 60312

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	17
DANN	Benign	0.89
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-0.18
Eigen_PC	Benign	0.085
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.26	N
PhyloP100		4.5
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.36	N
REVEL	Benign	0.097
Sift	Benign	0.58	T
Sift4G	Benign	0.67	T
Polyphen		0.016	B
Vest4		0.10
MutPred		0.51		Gain of MoRF binding (P = 0.0593)
MVP		0.33
MPC		0.23
ClinPred		0.17	T
GERP RS		5.8
Varity_R		0.078
gMVP		0.49
Mutation Taster		=66/34	polymorphism

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: rs139409404; hg19: chr7-110762841;