11-65546547-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001130144.3(LTBP3):​c.2248G>A​(p.Glu750Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,246 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

LTBP3
NM_001130144.3 missense

Scores

5
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.33
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.2721476).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LTBP3NM_001130144.3 linkuse as main transcriptc.2248G>A p.Glu750Lys missense_variant 16/28 ENST00000301873.11 NP_001123616.1
LTBP3NM_021070.4 linkuse as main transcriptc.2248G>A p.Glu750Lys missense_variant 16/27 NP_066548.2
LTBP3NM_001164266.1 linkuse as main transcriptc.1897G>A p.Glu633Lys missense_variant 16/27 NP_001157738.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LTBP3ENST00000301873.11 linkuse as main transcriptc.2248G>A p.Glu750Lys missense_variant 16/282 NM_001130144.3 ENSP00000301873 P1Q9NS15-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152246
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1449948
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
721762
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152246
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.26
BayesDel_addAF
Uncertain
0.10
D
BayesDel_noAF
Benign
-0.090
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.21
.;T;.;T;T
Eigen
Benign
-0.021
Eigen_PC
Benign
0.015
FATHMM_MKL
Benign
0.47
N
LIST_S2
Uncertain
0.88
D;T;D;D;D
M_CAP
Benign
0.067
D
MetaRNN
Benign
0.27
T;T;T;T;T
MetaSVM
Benign
-0.76
T
MutationAssessor
Benign
1.6
L;L;.;.;.
MutationTaster
Benign
0.67
D;D;D;D;N
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
-1.9
N;N;N;N;N
REVEL
Uncertain
0.46
Sift
Benign
0.31
T;T;T;T;T
Sift4G
Benign
0.57
T;T;T;.;T
Polyphen
0.83
P;D;B;D;.
Vest4
0.41
MutPred
0.49
Gain of ubiquitination at E750 (P = 0.0082);Gain of ubiquitination at E750 (P = 0.0082);.;.;.;
MVP
0.88
ClinPred
0.84
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.19
gMVP
0.59

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1554973844; hg19: chr11-65314018; API