NM_178839.5:c.1104G>A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_178839.5(LRRTM1):c.1104G>A(p.Glu368Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,612,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
LRRTM1
NM_178839.5 synonymous
NM_178839.5 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.61
Publications
3 publications found
Genes affected
LRRTM1 (HGNC:19408): (leucine rich repeat transmembrane neuronal 1) Predicted to be involved in regulation of postsynaptic density assembly and regulation of presynapse assembly. Predicted to act upstream of or within several processes, including long-term synaptic potentiation; negative regulation of receptor internalization; and positive regulation of synapse assembly. Located in endoplasmic reticulum and growth cone. Is active in GABA-ergic synapse. Is integral component of postsynaptic specialization membrane. [provided by Alliance of Genome Resources, Apr 2022]
CTNNA2 (HGNC:2510): (catenin alpha 2) Enables actin filament binding activity. Involved in negative regulation of Arp2/3 complex-mediated actin nucleation; regulation of neuron migration; and regulation of neuron projection development. Located in cytoplasm. Implicated in complex cortical dysplasia with other brain malformations. [provided by Alliance of Genome Resources, Apr 2022]
CTNNA2 Gene-Disease associations (from GenCC):
- cortical dysplasia, complex, with other brain malformations 9Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP7
Synonymous conserved (PhyloP=1.61 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_178839.5. 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 |
|---|---|---|---|---|---|---|---|---|---|
| LRRTM1 | NM_178839.5 | MANE Select | c.1104G>A | p.Glu368Glu | synonymous | Exon 2 of 2 | NP_849161.2 | Q86UE6 | |
| CTNNA2 | NM_001282597.3 | MANE Select | c.1057-90495C>T | intron | N/A | NP_001269526.1 | P26232-1 | ||
| CTNNA2 | NM_001282598.2 | c.1159-90495C>T | intron | N/A | NP_001269527.1 | P26232-5 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| LRRTM1 | ENST00000295057.4 | TSL:1 MANE Select | c.1104G>A | p.Glu368Glu | synonymous | Exon 2 of 2 | ENSP00000295057.3 | Q86UE6 | |
| CTNNA2 | ENST00000402739.9 | TSL:1 MANE Select | c.1057-90495C>T | intron | N/A | ENSP00000384638.4 | P26232-1 | ||
| CTNNA2 | ENST00000496558.5 | TSL:1 | c.1057-90495C>T | intron | N/A | ENSP00000419295.1 | P26232-2 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152210Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152210
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460528Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726568 show subpopulations
GnomAD4 exome
AF:
AC:
3
AN:
1460528
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
726568
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33470
American (AMR)
AF:
AC:
0
AN:
44686
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26108
East Asian (EAS)
AF:
AC:
0
AN:
39682
South Asian (SAS)
AF:
AC:
0
AN:
86226
European-Finnish (FIN)
AF:
AC:
0
AN:
52466
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
3
AN:
1111778
Other (OTH)
AF:
AC:
0
AN:
60346
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.558
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
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>80
Age
GnomAD4 genome 0.00000657 AC: 1AN: 152210Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74354 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152210
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
74354
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41458
American (AMR)
AF:
AC:
0
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5176
South Asian (SAS)
AF:
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
AC:
0
AN:
10620
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68044
Other (OTH)
AF:
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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