11-65557827-GC-GCC

Variant names:

• chr11-65557827-G-GC
• NM_001130144.3:c.132dupG

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_001130144.3(LTBP3):​c.132dupG​(p.Pro45AlafsTer149) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000381 in 1,311,146 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000038 (0 hom.)
• Consequence: LTBP3 NM_001130144.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138

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 Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTBP3	NM_001130144.3	c.132dupG	p.Pro45AlafsTer149	frameshift_variant	Exon 1 of 28	ENST00000301873.11	NP_001123616.1
LTBP3	NM_021070.4	c.132dupG	p.Pro45AlafsTer149	frameshift_variant	Exon 1 of 27		NP_066548.2
LTBP3	NM_001164266.1	c.-216dupG		5_prime_UTR_variant	Exon 1 of 27		NP_001157738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTBP3	ENST00000301873.11	c.132dupG	p.Pro45AlafsTer149	frameshift_variant	Exon 1 of 28	2	NM_001130144.3	ENSP00000301873.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000381 AC: 5 AN: 1311146 Hom.: 0 Cov.: 31 AF XY: 0.00000464 AC XY: 3 AN XY: 646342

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000325

Gnomad4 SAS exome AF: 0.0000142

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000288

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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: chr11-65325298;