Genetic Variant LTBP3:p.Arg1301Pro (chr11-65539090-C-G) – 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.3902G>C(p.Arg1301Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R1301H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

LTBP3
NM_001130144.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.64

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.3902G>C	p.Arg1301Pro	missense	Exon 28 of 28	NP_001123616.1	Q9NS15-1
LTBP3	NM_021070.4		c.3761G>C	p.Arg1254Pro	missense	Exon 27 of 27	NP_066548.2	Q9NS15-2
LTBP3	NM_001164266.1		c.3410G>C	p.Arg1137Pro	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.3902G>C	p.Arg1301Pro	missense	Exon 28 of 28	ENSP00000301873.5	Q9NS15-1
LTBP3	ENST00000322147.8	TSL:1	c.3761G>C	p.Arg1254Pro	missense	Exon 27 of 27	ENSP00000326647.4	Q9NS15-2
LTBP3	ENST00000528516.5	TSL:1	n.*3406G>C		non_coding_transcript_exon	Exon 27 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

0.27

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.88

M_CAP

Pathogenic

0.29

MetaRNN

Uncertain

0.53

MetaSVM

Uncertain

0.42

MutationAssessor

Benign

2.0

PhyloP100

2.6

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.57

Sift

Uncertain

0.0050

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.43

MutPred

0.45

Loss of MoRF binding (P = 3e-04)

MVP

0.86

ClinPred

0.99

GERP RS

3.9

Varity_R

0.65

gMVP

0.91

Mutation Taster

=32/68

disease causing

(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

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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