chr11-65553238-G-T

Variant names:

• chr11-65553238-G-T
• NM_001130144.3:c.989C>A

Variant summary

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

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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LTBP3 NM_001130144.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.84

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=0.4075541).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTBP3	NM_001130144.3	c.989C>A	p.Pro330Gln	missense_variant	Exon 5 of 28	ENST00000301873.11	NP_001123616.1
LTBP3	NM_021070.4	c.989C>A	p.Pro330Gln	missense_variant	Exon 5 of 27		NP_066548.2
LTBP3	NM_001164266.1	c.638C>A	p.Pro213Gln	missense_variant	Exon 5 of 27		NP_001157738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTBP3	ENST00000301873.11	c.989C>A	p.Pro330Gln	missense_variant	Exon 5 of 28	2	NM_001130144.3	ENSP00000301873.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.096	.;T;T;T
Eigen	Benign	-0.047
Eigen_PC	Benign	0.011
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.82	T;T;T;T
M_CAP	Uncertain	0.090	D
MetaRNN	Benign	0.41	T;T;T;T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	0.69	N;N;.;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.090	N;N;N;N
REVEL	Uncertain	0.33
Sift	Benign	0.053	T;D;D;T
Sift4G	Benign	0.12	T;T;.;.
Polyphen		0.72	P;P;P;.
Vest4		0.63
MutPred		0.61		Gain of catalytic residue at P330 (P = 0.0916);Gain of catalytic residue at P330 (P = 0.0916);.;.;
MVP		0.80
ClinPred		0.71	D
GERP RS		2.8
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.7
Varity_R		0.055
gMVP		0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-65320709;