rs147586574

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_003243.5(TGFBR3):c.55A>G(p.Thr19Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 1,611,870 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 33 hom. )

Consequence

TGFBR3
NM_003243.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.176

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]

TGFBR3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033077002).

BP6

Variant 1-91861477-T-C is Benign according to our data. Variant chr1-91861477-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 547813.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 560 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5 link	c.55A>G	p.Thr19Ala	missense_variant	Exon 2 of 17	ENST00000212355.9	NP_003234.2	Q03167-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9 link	c.55A>G	p.Thr19Ala	missense_variant	Exon 2 of 17	1	NM_003243.5	ENSP00000212355.4		Q03167-1

Frequencies

GnomAD3 genomes

AF:

0.00368

AC:

560

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0288

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00344

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00404

AC:

1016

AN:

251438

Hom.:

AF XY:

0.00395

AC XY:

537

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000173

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.0286

Gnomad NFE exome

AF:

0.00307

Gnomad OTH exome

AF:

0.00554

GnomAD4 exome

AF:

0.00306

AC:

4463

AN:

1459550

Hom.:

Cov.:

AF XY:

0.00297

AC XY:

2155

AN XY:

726298

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0284

Gnomad4 NFE exome

AF:

0.00251

Gnomad4 OTH exome

AF:

0.00240

GnomAD4 genome

AF:

0.00368

AC:

560

AN:

152320

Hom.:

Cov.:

AF XY:

0.00463

AC XY:

345

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0288

Gnomad4 NFE

AF:

0.00344

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00254

Hom.:

Bravo

AF:

0.00128

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00314

AC:

ExAC

AF:

0.00368

AC:

447

EpiCase

AF:

0.00234

EpiControl

AF:

0.00184

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

TGFBR3-related disorder

Benign:1

Feb 22, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Familial thoracic aortic aneurysm and aortic dissection

Benign:1

Nov 01, 2016

Center for Human Genetics, Inc, Center for Human Genetics, Inc

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.41

CADD

Benign

8.7

DANN

Benign

0.25

DEOGEN2

Benign

0.12

T;.;T;.;.

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.44

T;.;.;T;T

MetaRNN

Benign

0.0033

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L;L;L;.

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.53

N;N;N;N;D

REVEL

Benign

0.0070

Sift

Benign

0.10

T;T;T;T;D

Sift4G

Benign

0.82

T;T;T;T;.

Polyphen

0.10

B;B;B;B;.

Vest4

0.16

MVP

0.45

MPC

0.22

ClinPred

0.0042

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.038

gMVP

0.21

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over