chr10-66928097-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178011.5(LRRTM3):​c.1181C>T​(p.Pro394Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

LRRTM3
NM_178011.5 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.81
Variant links:
Genes affected
LRRTM3 (HGNC:19410): (leucine rich repeat transmembrane neuronal 3) Involved in presynapse assembly. Acts upstream of or within positive regulation of amyloid-beta formation. Is active in glutamatergic synapse. [provided by Alliance of Genome Resources, Apr 2022]
CTNNA3 (HGNC:2511): (catenin alpha 3) This gene encodes a protein that belongs to the vinculin/alpha-catenin family. The encoded protein plays a role in cell-cell adhesion in muscle cells. Mutations in this gene are associated with arrhythmogenic right ventricular dysplasia, familial 13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12393516).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LRRTM3NM_178011.5 linkuse as main transcriptc.1181C>T p.Pro394Leu missense_variant 2/3 ENST00000361320.5 NP_821079.3
CTNNA3NM_013266.4 linkuse as main transcriptc.1048-152573G>A intron_variant ENST00000433211.7 NP_037398.2
LOC101928961NR_111911.1 linkuse as main transcriptn.2718-17604G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LRRTM3ENST00000361320.5 linkuse as main transcriptc.1181C>T p.Pro394Leu missense_variant 2/31 NM_178011.5 ENSP00000355187 P1Q86VH5-1
CTNNA3ENST00000433211.7 linkuse as main transcriptc.1048-152573G>A intron_variant 1 NM_013266.4 ENSP00000389714 P1Q9UI47-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 19, 2024The c.1181C>T (p.P394L) alteration is located in exon 2 (coding exon 2) of the LRRTM3 gene. This alteration results from a C to T substitution at nucleotide position 1181, causing the proline (P) at amino acid position 394 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.061
BayesDel_addAF
Benign
-0.037
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.020
T
Eigen
Benign
0.0050
Eigen_PC
Uncertain
0.22
FATHMM_MKL
Benign
0.70
D
LIST_S2
Benign
0.84
T
M_CAP
Benign
0.048
D
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-0.44
T
MutationAssessor
Benign
0.49
N
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-0.87
N
REVEL
Uncertain
0.34
Sift
Benign
0.15
T
Sift4G
Uncertain
0.054
T
Polyphen
0.0010
B
Vest4
0.33
MutPred
0.28
Loss of glycosylation at P394 (P = 0.0113);
MVP
0.25
MPC
0.63
ClinPred
0.70
D
GERP RS
5.9
Varity_R
0.15
gMVP
0.64

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-68687855; API