11-65539084-C-CGGCGGCGCTGGGGAACGCAGGCCCCGTGCG

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP3

The NM_001130144.3(LTBP3):​c.3878_3907dupCGCACGGGGCCTGCGTTCCCCAGCGCCGCC​(p.Pro1293_Arg1302dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

LTBP3
NM_001130144.3 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.58
Variant links:
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP3
Nonframeshift variant in repetitive region in NM_001130144.3

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LTBP3NM_001130144.3 linkc.3878_3907dupCGCACGGGGCCTGCGTTCCCCAGCGCCGCC p.Pro1293_Arg1302dup conservative_inframe_insertion 28/28 ENST00000301873.11 NP_001123616.1 Q9NS15-1Q8WYU6
LTBP3NM_021070.4 linkc.3737_3766dupCGCACGGGGCCTGCGTTCCCCAGCGCCGCC p.Pro1246_Arg1255dup conservative_inframe_insertion 27/27 NP_066548.2 Q9NS15-2Q8WYU6
LTBP3NM_001164266.1 linkc.3386_3415dupCGCACGGGGCCTGCGTTCCCCAGCGCCGCC p.Pro1129_Arg1138dup conservative_inframe_insertion 27/27 NP_001157738.1 Q9NS15B9EG76Q8WYU6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LTBP3ENST00000301873.11 linkc.3878_3907dupCGCACGGGGCCTGCGTTCCCCAGCGCCGCC p.Pro1293_Arg1302dup conservative_inframe_insertion 28/282 NM_001130144.3 ENSP00000301873.5 Q9NS15-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Brachyolmia-amelogenesis imperfecta syndrome Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpMar 09, 2022In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals affected with LTBP3-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.3878_3907dup, results in the insertion of 10 amino acid(s) of the LTBP3 protein (p.Pro1293_Arg1302dup), but otherwise preserves the integrity of the reading frame. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-65306555; API