NM_003243.5:c.44C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_003243.5(TGFBR3):c.44C>T(p.Ser15Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,612,018 control chromosomes in the GnomAD database, including 11,638 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.13 ( 1643 hom., cov: 32)

Exomes 𝑓: 0.10 ( 9995 hom. )

Consequence

TGFBR3
NM_003243.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.65

Publications

42 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004665315).

BP6

Variant 1-91861488-G-A is Benign according to our data. Variant chr1-91861488-G-A is described in ClinVar as Benign. ClinVar VariationId is 3060183.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003243.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TGFBR3	NM_003243.5	MANE Select	c.44C>T	p.Ser15Phe	missense	Exon 2 of 17	NP_003234.2
TGFBR3	NM_001195683.2		c.44C>T	p.Ser15Phe	missense	Exon 2 of 17	NP_001182612.1
TGFBR3	NM_001195684.1		c.44C>T	p.Ser15Phe	missense	Exon 3 of 18	NP_001182613.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TGFBR3	ENST00000212355.9	TSL:1 MANE Select	c.44C>T	p.Ser15Phe	missense	Exon 2 of 17	ENSP00000212355.4
TGFBR3	ENST00000525962.5	TSL:1	c.44C>T	p.Ser15Phe	missense	Exon 1 of 16	ENSP00000436127.1
TGFBR3	ENST00000370399.6	TSL:1	c.44C>T	p.Ser15Phe	missense	Exon 3 of 18	ENSP00000359426.2

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19741

AN:

151990

Hom.:

1635

Cov.:

show subpopulations

Gnomad AFR

AF:

0.179

Gnomad AMI

AF:

0.0936

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.134

Gnomad EAS

AF:

0.397

Gnomad SAS

AF:

0.141

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0844

Gnomad OTH

AF:

0.121

GnomAD2 exomes

AF:

0.131

AC:

33006

AN:

251414

AF XY:

0.129

show subpopulations

Gnomad AFR exome

AF:

0.183

Gnomad AMR exome

AF:

0.126

Gnomad ASJ exome

AF:

0.132

Gnomad EAS exome

AF:

0.397

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.0856

Gnomad OTH exome

AF:

0.109

GnomAD4 exome

AF:

0.100

AC:

146296

AN:

1459910

Hom.:

9995

Cov.:

AF XY:

0.101

AC XY:

73264

AN XY:

726348

show subpopulations

African (AFR)

AF:

0.180

AC:

6009

AN:

33428

American (AMR)

AF:

0.128

AC:

5741

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.135

AC:

3524

AN:

26114

East Asian (EAS)

AF:

0.417

AC:

16534

AN:

39654

South Asian (SAS)

AF:

0.135

AC:

11603

AN:

86214

European-Finnish (FIN)

AF:

0.110

AC:

5856

AN:

53392

Middle Eastern (MID)

AF:

0.0770

AC:

444

AN:

5766

European-Non Finnish (NFE)

AF:

0.0809

AC:

89860

AN:

1110316

Other (OTH)

AF:

0.112

AC:

6725

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

6124

12248

18373

24497

30621

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3604

7208

10812

14416

18020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.130

AC:

19782

AN:

152108

Hom.:

1643

Cov.:

AF XY:

0.132

AC XY:

9792

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.180

AC:

7452

AN:

41460

American (AMR)

AF:

0.121

AC:

1848

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.134

AC:

464

AN:

3466

East Asian (EAS)

AF:

0.397

AC:

2057

AN:

5178

South Asian (SAS)

AF:

0.140

AC:

674

AN:

4808

European-Finnish (FIN)

AF:

0.110

AC:

1167

AN:

10588

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0844

AC:

5740

AN:

68008

Other (OTH)

AF:

0.127

AC:

269

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

860

1720

2579

3439

4299

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

220

440

660

880

1100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.105

Hom.:

4864

Bravo

AF:

0.135

TwinsUK

AF:

0.0833

AC:

309

ALSPAC

AF:

0.0838

AC:

323

ESP6500AA

AF:

0.175

AC:

771

ESP6500EA

AF:

0.0848

AC:

729

ExAC

AF:

0.131

AC:

15872

Asia WGS

AF:

0.236

AC:

819

AN:

3478

EpiCase

AF:

0.0852

EpiControl

AF:

0.0836

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TGFBR3-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.11

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.83

MetaRNN

Benign

0.0047

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

PhyloP100

1.7

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.25

REVEL

Benign

0.094

Sift

Benign

0.17

Sift4G

Benign

0.70

Polyphen

0.0

Vest4

0.12

MPC

0.25

ClinPred

0.0078

GERP RS

3.2

PromoterAI

0.00040

Neutral

(source)

Varity_R

0.058

gMVP

0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over