chr2-77518535-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_001134745.3(LRRTM4):c.1334T>C(p.Val445Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,310 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
LRRTM4
NM_001134745.3 missense
NM_001134745.3 missense
Scores
6
7
5
Clinical Significance
Conservation
PhyloP100: 9.32
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 Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRRTM4 | NM_001134745.3 | c.1334T>C | p.Val445Ala | missense_variant | 3/4 | ENST00000409884.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRRTM4 | ENST00000409884.6 | c.1334T>C | p.Val445Ala | missense_variant | 3/4 | 1 | NM_001134745.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152068Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000403 AC: 1AN: 248204Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134622
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GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461242Hom.: 0 Cov.: 34 AF XY: 0.00000688 AC XY: 5AN XY: 726902
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GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152068Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74274
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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 | Sep 26, 2022 | The c.1334T>C (p.V445A) alteration is located in exon 3 (coding exon 2) of the LRRTM4 gene. This alteration results from a T to C substitution at nucleotide position 1334, causing the valine (V) at amino acid position 445 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T;T;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;N;N
REVEL
Uncertain
Sift
Benign
D;D;D;D;D
Sift4G
Uncertain
T;T;T;T;T
Polyphen
0.90, 0.94
.;P;P;P;P
Vest4
MutPred
0.40
.;Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);.;
MVP
MPC
1.7
ClinPred
D
GERP RS
Varity_R
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