dbSNP rs1360222605: LTBP3:p.Pro1299Leu (chr11-65539096-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 3.91

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: G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
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

LTBP3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.3896C>T	p.Pro1299Leu	missense	Exon 28 of 28	NP_001123616.1	Q9NS15-1
LTBP3	NM_021070.4		c.3755C>T	p.Pro1252Leu	missense	Exon 27 of 27	NP_066548.2	Q9NS15-2
LTBP3	NM_001164266.1		c.3404C>T	p.Pro1135Leu	missense	Exon 27 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.3896C>T	p.Pro1299Leu	missense	Exon 28 of 28	ENSP00000301873.5	Q9NS15-1
LTBP3	ENST00000322147.8	TSL:1	c.3755C>T	p.Pro1252Leu	missense	Exon 27 of 27	ENSP00000326647.4	Q9NS15-2
LTBP3	ENST00000528516.5	TSL:1	n.*3400C>T		non_coding_transcript_exon	Exon 27 of 27	ENSP00000432350.1	E9PRF2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

86236

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

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

African (AFR)

AF:

0.00

AC:

AN:

25602

American (AMR)

AF:

0.00

AC:

AN:

24886

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21868

East Asian (EAS)

AF:

0.00

AC:

AN:

28622

South Asian (SAS)

AF:

0.00

AC:

AN:

70980

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33840

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3912

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1024442

Other (OTH)

AF:

0.00

AC:

AN:

52268

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Brachyolmia-amelogenesis imperfecta syndrome (1)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.63

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.91

M_CAP

Pathogenic

0.48

MetaRNN

Uncertain

0.45

MetaSVM

Uncertain

0.61

MutationAssessor

Benign

1.9

PhyloP100

3.9

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-5.9

REVEL

Uncertain

0.58

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.011

Polyphen

0.97

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

Mutation Taster

=77/23

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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