chr10-66928155-G-T
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_178011.5(LRRTM3):c.1239G>T(p.Glu413Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,614,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
LRRTM3
NM_178011.5 missense
NM_178011.5 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 2.62
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 Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.17171782).
BS2
High AC in GnomAdExome4 at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LRRTM3 | NM_178011.5 | c.1239G>T | p.Glu413Asp | missense_variant | 2/3 | ENST00000361320.5 | NP_821079.3 | |
CTNNA3 | NM_013266.4 | c.1048-152631C>A | intron_variant | ENST00000433211.7 | NP_037398.2 | |||
LOC101928961 | NR_111911.1 | n.2718-17662C>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LRRTM3 | ENST00000361320.5 | c.1239G>T | p.Glu413Asp | missense_variant | 2/3 | 1 | NM_178011.5 | ENSP00000355187 | P1 | |
CTNNA3 | ENST00000433211.7 | c.1048-152631C>A | intron_variant | 1 | NM_013266.4 | ENSP00000389714 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152130Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000279 AC: 7AN: 250460Hom.: 0 AF XY: 0.0000443 AC XY: 6AN XY: 135590
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GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461792Hom.: 0 Cov.: 32 AF XY: 0.0000151 AC XY: 11AN XY: 727184
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152248Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74446
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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 submitter | clinical testing | Ambry Genetics | Dec 20, 2023 | The c.1239G>T (p.E413D) alteration is located in exon 2 (coding exon 2) of the LRRTM3 gene. This alteration results from a G to T substitution at nucleotide position 1239, causing the glutamic acid (E) at amino acid position 413 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Loss of sheet (P = 0.0181);
MVP
MPC
ClinPred
D
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at