11-65557854-CCAGCAGCAGCAGCAGCAGCAG-CCAGCAGCAGCAGCAG

Position:

• chr11-65557854-CCAGCAGCAGCAGCAGCAGCAG-CCAGCAGCAGCAGCAG

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001130144.3(LTBP3):​c.100_105delCTGCTG​(p.Leu34_Leu35del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000153 in 1,319,066 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000094 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: LTBP3 NM_001130144.3 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 0.420

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTBP3	NM_001130144.3	c.100_105delCTGCTG	p.Leu34_Leu35del	conservative_inframe_deletion	1/28	ENST00000301873.11	NP_001123616.1
LTBP3	NM_021070.4	c.100_105delCTGCTG	p.Leu34_Leu35del	conservative_inframe_deletion	1/27		NP_066548.2
LTBP3	NM_001164266.1	c.-248_-243delCTGCTG		5_prime_UTR_variant	1/27		NP_001157738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LTBP3	ENST00000301873.11	c.100_105delCTGCTG	p.Leu34_Leu35del	conservative_inframe_deletion	1/28	2	NM_001130144.3	ENSP00000301873.5

Frequencies

GnomAD3 genomes AF: 0.0000939 AC: 14 AN: 149158 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000733

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000665

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000780

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000103

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000747

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000161 AC: 188 AN: 1169818 Hom.: 0 AF XY: 0.000187 AC XY: 107 AN XY: 571532

Gnomad4 AFR exome AF: 0.000167

Gnomad4 AMR exome AF: 0.000471

Gnomad4 ASJ exome AF: 0.000226

Gnomad4 EAS exome AF: 0.000511

Gnomad4 SAS exome AF: 0.000627

Gnomad4 FIN exome AF: 0.000151

Gnomad4 NFE exome AF: 0.000117

Gnomad4 OTH exome AF: 0.000235

GnomAD4 genome AF: 0.0000938 AC: 14 AN: 149248 Hom.: 0 Cov.: 27 AF XY: 0.0000824 AC XY: 6 AN XY: 72844

Gnomad4 AFR AF: 0.0000731

Gnomad4 AMR AF: 0.0000665

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000783

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000103

Gnomad4 NFE AF: 0.0000747

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

Submissions by phenotype

Brachyolmia-amelogenesis imperfecta syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 22, 2023

This variant, c.100_105del, results in the deletion of 2 amino acid(s) of the LTBP3 protein (p.Leu34_Leu35del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with LTBP3-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In 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. -

LTBP3-related disorder Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 14, 2024

The LTBP3 c.100_105del6 variant is predicted to result in an in-frame deletion (p.Leu34_Leu35del). To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs71036212; hg19: chr11-65325325;