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rs75857126

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_004612.4(TGFBR1):c.440T>C(p.Ile147Thr) variant causes a missense change involving the alteration of a 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.

Frequency

Genomes: not found (cov: 32)

Consequence

TGFBR1
NM_004612.4 missense

Scores

2
7
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.02
Variant links:
Genes affected
TGFBR1 (HGNC:11772): (transforming growth factor beta receptor 1) The protein encoded by this gene forms a heteromeric complex with type II TGF-beta receptors when bound to TGF-beta, transducing the TGF-beta signal from the cell surface to the cytoplasm. The encoded protein is a serine/threonine protein kinase. Mutations in this gene have been associated with Loeys-Dietz aortic aneurysm syndrome (LDAS). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, TGFBR1

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TGFBR1NM_004612.4 linkuse as main transcriptc.440T>C p.Ile147Thr missense_variant 3/9 ENST00000374994.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TGFBR1ENST00000374994.9 linkuse as main transcriptc.440T>C p.Ile147Thr missense_variant 3/91 NM_004612.4 P4P36897-1

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
0.32
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.050
Cadd
Benign
22
Dann
Uncertain
0.99
DEOGEN2
Benign
0.023
T;T;T;.;.;.;T
Eigen
Uncertain
0.33
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.97
D;D;D;D;D;D;D
M_CAP
Benign
0.024
T
MetaRNN
Uncertain
0.43
T;T;T;T;T;T;T
MetaSVM
Benign
-0.71
T
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-0.63
N;N;N;N;N;N;.
REVEL
Benign
0.22
Sift
Benign
0.30
T;T;T;T;D;T;.
Sift4G
Benign
0.15
T;T;T;T;D;T;T
Polyphen
0.0070, 0.83
.;.;B;.;P;.;.
Vest4
0.74, 0.69, 0.69
MutPred
0.57
.;.;Loss of stability (P = 0.0447);.;.;.;.;
MVP
0.70
MPC
0.66
ClinPred
0.60
D
GERP RS
6.0
Varity_R
0.055
gMVP
0.53

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

LitVar

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

Other links and lift over

dbSNP: rs75857126; hg19: chr9-101894887; API