chr1-91712395-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003243.5(TGFBR3):ā€‹c.2014A>Gā€‹(p.Lys672Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,614,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 33)
Exomes š‘“: 0.000034 ( 0 hom. )

Consequence

TGFBR3
NM_003243.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.46
Variant links:
Genes affected
TGFBR3 (HGNC:11774): (transforming growth factor beta receptor 3) This locus encodes the transforming growth factor (TGF)-beta type III receptor. The encoded receptor is a membrane proteoglycan that often functions as a co-receptor with other TGF-beta receptor superfamily members. Ectodomain shedding produces soluble TGFBR3, which may inhibit TGFB signaling. Decreased expression of this receptor has been observed in various cancers. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene.[provided by RefSeq, Sep 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.049329758).
BS2
High AC in GnomAdExome4 at 49 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TGFBR3NM_003243.5 linkuse as main transcriptc.2014A>G p.Lys672Glu missense_variant 13/17 ENST00000212355.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TGFBR3ENST00000212355.9 linkuse as main transcriptc.2014A>G p.Lys672Glu missense_variant 13/171 NM_003243.5 P3Q03167-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152238
Hom.:
0
Cov.:
33
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:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000716
AC:
18
AN:
251298
Hom.:
0
AF XY:
0.000125
AC XY:
17
AN XY:
135810
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000490
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000335
AC:
49
AN:
1461878
Hom.:
0
Cov.:
33
AF XY:
0.0000509
AC XY:
37
AN XY:
727238
show subpopulations
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:
0.000429
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000989
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152238
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74384
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:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.0000659
AC:
8

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 06, 2021The c.2014A>G (p.K672E) alteration is located in exon 13 (coding exon 12) of the TGFBR3 gene. This alteration results from a A to G substitution at nucleotide position 2014, causing the lysine (K) at amino acid position 672 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.085
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
20
DANN
Benign
0.97
DEOGEN2
Benign
0.28
T;.;T;.
Eigen
Benign
-0.19
Eigen_PC
Benign
-0.0055
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Benign
0.74
T;.;.;T
M_CAP
Benign
0.0042
T
MetaRNN
Benign
0.049
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
L;.;L;.
MutationTaster
Benign
0.92
N;N;N;N
PrimateAI
Benign
0.24
T
PROVEAN
Benign
0.12
N;N;N;N
REVEL
Benign
0.032
Sift
Benign
0.46
T;T;T;T
Sift4G
Benign
0.83
T;T;T;T
Polyphen
0.0010
B;B;B;B
Vest4
0.070
MutPred
0.40
Loss of ubiquitination at K672 (P = 0.0161);.;Loss of ubiquitination at K672 (P = 0.0161);.;
MVP
0.53
MPC
0.32
ClinPred
0.076
T
GERP RS
3.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.14
gMVP
0.47

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: rs748078614; hg19: chr1-92177952; API