NM_178839.5:c.102C>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.102C>A(p.Ala34Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,606,736 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: 32)
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: 1.58
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: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
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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=-0.61).
BP7
Synonymous conserved (PhyloP=1.58 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
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| LRRTM1 | NM_178839.5 | MANE Select | c.102C>A | p.Ala34Ala | synonymous | Exon 2 of 2 | NP_849161.2 | ||
| CTNNA2 | NM_001282597.3 | MANE Select | c.1057-89493G>T | intron | N/A | NP_001269526.1 | |||
| CTNNA2 | NM_001282598.2 | c.1159-89493G>T | intron | N/A | NP_001269527.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| LRRTM1 | ENST00000295057.4 | TSL:1 MANE Select | c.102C>A | p.Ala34Ala | synonymous | Exon 2 of 2 | ENSP00000295057.3 | ||
| LRRTM1 | ENST00000417012.5 | TSL:1 | n.102C>A | non_coding_transcript_exon | Exon 2 of 3 | ENSP00000393562.1 | |||
| LRRTM1 | ENST00000433224.1 | TSL:1 | n.102C>A | non_coding_transcript_exon | Exon 2 of 3 | ENSP00000414523.1 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152164
Hom.:
Cov.:
32
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: 0.00000206 AC: 3AN: 1454572Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 2AN XY: 722758 show subpopulations
GnomAD4 exome
AF:
AC:
3
AN:
1454572
Hom.:
Cov.:
31
AF XY:
AC XY:
2
AN XY:
722758
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33326
American (AMR)
AF:
AC:
0
AN:
44194
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25694
East Asian (EAS)
AF:
AC:
0
AN:
39576
South Asian (SAS)
AF:
AC:
0
AN:
85160
European-Finnish (FIN)
AF:
AC:
0
AN:
52348
Middle Eastern (MID)
AF:
AC:
0
AN:
5730
European-Non Finnish (NFE)
AF:
AC:
3
AN:
1108484
Other (OTH)
AF:
AC:
0
AN:
60060
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
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
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50-55
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60-65
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>80
Age
GnomAD4 genome 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74326 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152164
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74326
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41446
American (AMR)
AF:
AC:
0
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5160
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:
68030
Other (OTH)
AF:
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
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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