Genetic Variant LTBP3:p.Pro330Gln (chr11-65553238-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001130144.3(LTBP3):c.989C>A(p.Pro330Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P330L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

LTBP3
NM_001130144.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.84

Publications

0 publications found

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 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
Acromicric dysplasia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
geleophysic dysplasia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LTBP3 links:

ENSG00000302197 (HGNC:):

ENSG00000302197 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4075541).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130144.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LTBP3	NM_001130144.3	MANE Select	c.989C>A	p.Pro330Gln	missense	Exon 5 of 28	NP_001123616.1	Q9NS15-1
LTBP3	NM_021070.4		c.989C>A	p.Pro330Gln	missense	Exon 5 of 27	NP_066548.2	Q9NS15-2
LTBP3	NM_001164266.1		c.638C>A	p.Pro213Gln	missense	Exon 5 of 27	NP_001157738.1	Q9NS15

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LTBP3	ENST00000301873.11	TSL:2 MANE Select	c.989C>A	p.Pro330Gln	missense	Exon 5 of 28	ENSP00000301873.5	Q9NS15-1
LTBP3	ENST00000322147.8	TSL:1	c.989C>A	p.Pro330Gln	missense	Exon 5 of 27	ENSP00000326647.4	Q9NS15-2
LTBP3	ENST00000528516.5	TSL:1	n.*634C>A		non_coding_transcript_exon	Exon 5 of 27	ENSP00000432350.1	E9PRF2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.096

Eigen

Benign

-0.047

Eigen_PC

Benign

0.011

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.82

M_CAP

Uncertain

0.090

MetaRNN

Benign

0.41

MetaSVM

Benign

-0.39

MutationAssessor

Benign

0.69

PhyloP100

4.8

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.090

REVEL

Uncertain

0.33

Sift

Benign

0.053

Sift4G

Benign

0.12

Polyphen

0.72

Vest4

0.63

MutPred

0.61

Gain of catalytic residue at P330 (P = 0.0916)

MVP

0.80

ClinPred

0.71

GERP RS

2.8

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.7

Varity_R

0.055

gMVP

0.46

Mutation Taster

=84/16

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over