rs1554974135
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001130144.3(LTBP3):c.2087C>G(p.Ser696Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Consequence
LTBP3
NM_001130144.3 missense
NM_001130144.3 missense
Scores
1
3
15
Clinical Significance
Conservation
PhyloP100: 2.23
Genes affected
LTBP3 (HGNC:6716): (latent transforming growth factor beta binding protein 3) The protein encoded by this gene forms a complex with transforming growth factor beta (TGF-beta) proteins and may be involved in their subcellular localization. Activation of this complex requires removal of the encoded binding protein. This protein also may play a structural role in the extracellular matrix. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.184735).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LTBP3 | NM_001130144.3 | c.2087C>G | p.Ser696Cys | missense_variant | 14/28 | ENST00000301873.11 | NP_001123616.1 | |
LTBP3 | NM_021070.4 | c.2087C>G | p.Ser696Cys | missense_variant | 14/27 | NP_066548.2 | ||
LTBP3 | NM_001164266.1 | c.1736C>G | p.Ser579Cys | missense_variant | 14/27 | NP_001157738.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LTBP3 | ENST00000301873.11 | c.2087C>G | p.Ser696Cys | missense_variant | 14/28 | 2 | NM_001130144.3 | ENSP00000301873.5 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
ClinVar
Significance: Uncertain significance
Submissions summary: Pathogenic:1Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Geleophysic dysplasia 3 Pathogenic:1Uncertain:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 13, 2017 | - - |
Uncertain significance, criteria provided, single submitter | curation | SIB Swiss Institute of Bioinformatics | Oct 15, 2018 | This variant is interpreted as Uncertain Significance - Conflicting Evidence, for Geleophysic dysplasia 3, autosomal dominant. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PP1 => Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (https://www.ncbi.nlm.nih.gov/pubmed/27068007). BS3-Supporting => BS3 downgraded in strength to supporting No effect on TGF-beta secretion (https://www.ncbi.nlm.nih.gov/pubmed/27068007). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;T;.;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T;D;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.;.;.
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D;D
Sift4G
Benign
T;T;T;.;T
Polyphen
P;D;P;D;.
Vest4
MutPred
Loss of glycosylation at S696 (P = 0.0308);Loss of glycosylation at S696 (P = 0.0308);.;.;.;
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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