11-65539063-GGGCGGCGTC-GGGCGGCGTCGGCGGCGTCGGCGGCGTC

Variant names:

• chr11-65539063-G-GGGCGGCGTCGGCGGCGTC
• rs539110133
• ENST00000528516.5:n.*3415_*3432dupGACGCCGCCGACGCCGCC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000528516.5(LTBP3):​n.*3415_*3432dupGACGCCGCCGACGCCGCC variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000825 in 1,212,692 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: LTBP3 ENST00000528516.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.174
• Publications: 0 publications found

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]

LTBP3 Gene-Disease associations (from GenCC):

• brachyolmia-amelogenesis imperfecta syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• geleophysic dysplasia 3

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• Acromicric dysplasia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• geleophysic dysplasia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTBP3	NM_001130144.3	c.3911_*16dupGACGCCGCCGACGCCGCC		3_prime_UTR_variant	Exon 28 of 28	ENST00000301873.11	NP_001123616.1
LTBP3	NM_021070.4	c.3770_*16dupGACGCCGCCGACGCCGCC		3_prime_UTR_variant	Exon 27 of 27		NP_066548.2
LTBP3	NM_001164266.1	c.3419_*16dupGACGCCGCCGACGCCGCC		3_prime_UTR_variant	Exon 27 of 27		NP_001157738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTBP3	ENST00000301873.11	c.3911_*16dupGACGCCGCCGACGCCGCC		3_prime_UTR_variant	Exon 28 of 28	2	NM_001130144.3	ENSP00000301873.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.25e-7 AC: 1 AN: 1212692 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 589414

African (AFR) AF: 0.00 AC: 0 AN: 23068

American (AMR) AF: 0.00 AC: 0 AN: 12450

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17208

East Asian (EAS) AF: 0.00 AC: 0 AN: 27340

South Asian (SAS) AF: 0.00 AC: 0 AN: 57518

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29816

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3436

European-Non Finnish (NFE) AF: 0.00000101 AC: 1 AN: 992992

Other (OTH) AF: 0.00 AC: 0 AN: 48864

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.17

Splicing

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

Other links and lift over

dbSNP: rs539110133; hg19: chr11-65306534;