11-65551473-G-C

Variant names:

• chr11-65551473-G-C
• NM_001130144.3:c.1550C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001130144.3(LTBP3):​c.1550C>G​(p.Pro517Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. P517L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LTBP3 NM_001130144.3 missense, splice_region
• Scores: Splicing: ADA: 0.7978
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.38

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26762268).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTBP3	NM_001130144.3	c.1550C>G	p.Pro517Arg	missense_variant, splice_region_variant	Exon 10 of 28	ENST00000301873.11	NP_001123616.1
LTBP3	NM_021070.4	c.1550C>G	p.Pro517Arg	missense_variant, splice_region_variant	Exon 10 of 27		NP_066548.2
LTBP3	NM_001164266.1	c.1199C>G	p.Pro400Arg	missense_variant, splice_region_variant	Exon 10 of 27		NP_001157738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTBP3	ENST00000301873.11	c.1550C>G	p.Pro517Arg	missense_variant, splice_region_variant	Exon 10 of 28	2	NM_001130144.3	ENSP00000301873.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	.;D;T
Eigen	Benign	-0.012
Eigen_PC	Benign	0.093
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.0	M;M;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Uncertain	0.31
Sift	Uncertain	0.0050	D;D;D
Sift4G	Uncertain	0.0040	D;D;.
Polyphen		0.61	P;P;P
Vest4		0.69
MutPred		0.34		Loss of glycosylation at T514 (P = 0.0398);Loss of glycosylation at T514 (P = 0.0398);.;
MVP		0.72
ClinPred		0.78	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.80
dbscSNV1_RF	Benign	0.56
SpliceAI score (max)		0.16		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: chr11-65318944;