chr2-77518500-G-C
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001134745.3(LRRTM4):āc.1369C>Gā(p.Leu457Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,613,312 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00011 ( 0 hom., cov: 32)
Exomes š: 0.00010 ( 0 hom. )
Consequence
LRRTM4
NM_001134745.3 missense
NM_001134745.3 missense
Scores
3
10
5
Clinical Significance
Conservation
PhyloP100: 10.0
Genes affected
LRRTM4 (HGNC:19411): (leucine rich repeat transmembrane neuronal 4) Predicted to enable heparan sulfate proteoglycan binding activity. Predicted to be involved in regulation of synapse assembly. Predicted to act upstream of or within AMPA glutamate receptor clustering; positive regulation of synapse assembly; and regulation of presynaptic membrane organization. Predicted to be located in postsynaptic membrane. Predicted to be part of AMPA glutamate receptor complex. Predicted to be active in extracellular matrix; extracellular space; and glutamatergic synapse. Predicted to be integral component of postsynaptic density membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAd4 at 16 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRRTM4 | NM_001134745.3 | c.1369C>G | p.Leu457Val | missense_variant | 3/4 | ENST00000409884.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRRTM4 | ENST00000409884.6 | c.1369C>G | p.Leu457Val | missense_variant | 3/4 | 1 | NM_001134745.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152048Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000806 AC: 20AN: 248166Hom.: 0 AF XY: 0.0000892 AC XY: 12AN XY: 134590
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GnomAD4 exome AF: 0.000101 AC: 148AN: 1461264Hom.: 0 Cov.: 34 AF XY: 0.000121 AC XY: 88AN XY: 726898
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GnomAD4 genome AF: 0.000105 AC: 16AN: 152048Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74252
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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 | May 08, 2023 | The c.1369C>G (p.L457V) alteration is located in exon 3 (coding exon 2) of the LRRTM4 gene. This alteration results from a C to G substitution at nucleotide position 1369, causing the leucine (L) at amino acid position 457 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;T;.;T
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T;T;T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;N;N
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D
Polyphen
1.0, 1.0
.;D;D;D;D
Vest4
MVP
MPC
1.5
ClinPred
T
GERP RS
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gMVP
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