11-65557854-CCAGCAGCAGCAGCAGCAGCAG-CCAGCAGCAG

Position:

• chr11-65557854-CCAGCAGCAGCAGCAGCAGCAG-CCAGCAGCAG

Variant summary

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

The NM_001130144.3(LTBP3):​c.94_105delCTGCTGCTGCTG​(p.Leu32_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 0.0000295 in 1,320,176 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 27)
  • Exomes 𝑓: 0.000031 (0 hom.)
• Consequence: LTBP3 NM_001130144.3 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.773

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.94_105delCTGCTGCTGCTG	p.Leu32_Leu35del	conservative_inframe_deletion	1/28	ENST00000301873.11	NP_001123616.1
LTBP3	NM_021070.4	c.94_105delCTGCTGCTGCTG	p.Leu32_Leu35del	conservative_inframe_deletion	1/27		NP_066548.2
LTBP3	NM_001164266.1	c.-254_-243delCTGCTGCTGCTG		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.94_105delCTGCTGCTGCTG	p.Leu32_Leu35del	conservative_inframe_deletion	1/28	2	NM_001130144.3	ENSP00000301873.5

Frequencies

GnomAD3 genomes AF: 0.0000201 AC: 3 AN: 149160 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000299

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000307 AC: 36 AN: 1171016 Hom.: 0 AF XY: 0.0000350 AC XY: 20 AN XY: 572178

Gnomad4 AFR exome AF: 0.0000836

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.000113

Gnomad4 NFE exome AF: 0.0000261

Gnomad4 OTH exome AF: 0.0000213

GnomAD4 genome AF: 0.0000201 AC: 3 AN: 149160 Hom.: 0 Cov.: 27 AF XY: 0.0000137 AC XY: 1 AN XY: 72742

Gnomad4 AFR AF: 0.0000244

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000299

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Brachyolmia-amelogenesis imperfecta syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 23, 2023

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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.94_105del, results in the deletion of 4 amino acid(s) of the LTBP3 protein (p.Leu32_Leu35del), but otherwise preserves the integrity of the reading frame. -

Brachyolmia-amelogenesis imperfecta syndrome;C4540511:Geleophysic dysplasia 3 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Sep 28, 2021

- -

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;