rs267607229
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The NM_001042545.2(LTBP4):c.730T>G(p.Cys244Gly) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Consequence
LTBP4
NM_001042545.2 missense
NM_001042545.2 missense
Scores
11
5
2
Clinical Significance
Conservation
PhyloP100: 1.96
Genes affected
LTBP4 (HGNC:6717): (latent transforming growth factor beta binding protein 4) The protein encoded by this gene binds transforming growth factor beta (TGFB) as it is secreted and targeted to the extracellular matrix. TGFB is biologically latent after secretion and insertion into the extracellular matrix, and sheds TGFB and other proteins upon activation. Defects in this gene may be a cause of cutis laxa and severe pulmonary, gastrointestinal, and urinary abnormalities. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.966
PP5
?
Variant 19-40605768-T-G is Pathogenic according to our data. Variant chr19-40605768-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 5398.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LTBP4 | NM_001042545.2 | c.730T>G | p.Cys244Gly | missense_variant | 4/30 | ENST00000396819.8 | |
LTBP4 | NM_001042544.1 | c.931T>G | p.Cys311Gly | missense_variant | 7/33 | ||
LTBP4 | NM_003573.2 | c.820T>G | p.Cys274Gly | missense_variant | 7/33 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LTBP4 | ENST00000396819.8 | c.730T>G | p.Cys244Gly | missense_variant | 4/30 | 1 | NM_001042545.2 | P3 | |
LTBP4 | ENST00000308370.11 | c.931T>G | p.Cys311Gly | missense_variant | 7/33 | 1 | A2 | ||
LTBP4 | ENST00000204005.13 | c.820T>G | p.Cys274Gly | missense_variant | 7/33 | 1 | A2 | ||
LTBP4 | ENST00000598717.5 | n.429-5606T>G | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 2009 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
T;D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
0.99
.;D;.
Vest4
MutPred
0.83
.;Gain of disorder (P = 0.0378);.;
MVP
MPC
2.1
ClinPred
D
GERP RS
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