11-65557854-C-CCAGCAGCAGCAGCAGCAG

Position:

• chr11-65557854-C-CCAGCAGCAGCAGCAGCAG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001130144.3(LTBP3):​c.88_105dupCTGCTGCTGCTGCTGCTG​(p.Leu30_Leu35dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000067 in 149,162 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 27)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LTBP3 NM_001130144.3 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.342

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTBP3	NM_001130144.3	c.88_105dupCTGCTGCTGCTGCTGCTG	p.Leu30_Leu35dup	conservative_inframe_insertion	1/28	ENST00000301873.11	NP_001123616.1
LTBP3	NM_021070.4	c.88_105dupCTGCTGCTGCTGCTGCTG	p.Leu30_Leu35dup	conservative_inframe_insertion	1/27		NP_066548.2
LTBP3	NM_001164266.1	c.-260_-243dupCTGCTGCTGCTGCTGCTG		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.88_105dupCTGCTGCTGCTGCTGCTG	p.Leu30_Leu35dup	conservative_inframe_insertion	1/28	2	NM_001130144.3	ENSP00000301873.5

Frequencies

GnomAD3 genomes AF: 0.00000670 AC: 1 AN: 149162 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.000491

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 8.54e-7 AC: 1 AN: 1171094 Hom.: 0 Cov.: 26 AF XY: 0.00000175 AC XY: 1 AN XY: 572218

Gnomad4 AFR exome AF: 0.0000417

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000670 AC: 1 AN: 149162 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 72744

Gnomad4 AFR AF: 0.00

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: 0.00

Gnomad4 OTH AF: 0.000491

ClinVar

Not reported in ClinVar

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;