Variant 11-65539096-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001130144.3(LTBP3):c.3896C>T(p.Pro1299Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P1299P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LTBP3
NM_001130144.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.91

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
LTBP3	NM_001130144.3 linkuse as main transcript	c.3896C>T	p.Pro1299Leu	missense_variant	28/28	ENST00000301873.11
LTBP3	NM_021070.4 linkuse as main transcript	c.3755C>T	p.Pro1252Leu	missense_variant	27/27
LTBP3	NM_001164266.1 linkuse as main transcript	c.3404C>T	p.Pro1135Leu	missense_variant	27/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTBP3	ENST00000301873.11 linkuse as main transcript	c.3896C>T	p.Pro1299Leu	missense_variant	28/28	2	NM_001130144.3	P1	Q9NS15-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1286420

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

630600

Gnomad4 AFR exome

AF:

0.00

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

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 24, 2021

The p.P1299L variant (also known as c.3896C>T), located in coding exon 28 of the LTBP3 gene, results from a C to T substitution at nucleotide position 3896. The proline at codon 1299 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.63

.;D;.;.;.

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.91

D;D;D;D;D

M_CAP

Pathogenic

0.48

MetaRNN

Uncertain

0.45

T;T;T;T;T

MetaSVM

Uncertain

0.61

MutationAssessor

Benign

1.9

.;L;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-5.9

D;D;D;D;D

REVEL

Uncertain

0.58

Sift

Uncertain

0.0010

D;D;D;D;D

Sift4G

Uncertain

0.011

D;D;D;D;T

Polyphen

0.97

D;D;.;.;P

Vest4

0.44

MutPred

0.46

.;Gain of stability (P = 0.0591);.;.;.;

MVP

0.88

ClinPred

0.99

GERP RS

4.9

Varity_R

0.32

gMVP

0.87

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over