Variant 1-91861488-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR3	NM_003243.5 linkuse as main transcript	c.44C>T	p.Ser15Phe	missense_variant	2/17	ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9 linkuse as main transcript	c.44C>T	p.Ser15Phe	missense_variant	2/17	1	NM_003243.5	ENSP00000212355	P3	Q03167-1

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

GnomAD3 exomes

AF:

0.131

AC:

33006

AN:

251414

Hom.:

3003

AF XY:

0.129

AC XY:

17493

AN XY:

135892

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 SAS exome

AF:

0.137

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

Gnomad4 AFR exome

AF:

0.180

Gnomad4 AMR exome

AF:

0.128

Gnomad4 ASJ exome

AF:

0.135

Gnomad4 EAS exome

AF:

0.417

Gnomad4 SAS exome

AF:

0.135

Gnomad4 FIN exome

AF:

0.110

Gnomad4 NFE exome

AF:

0.0809

Gnomad4 OTH exome

AF:

0.112

GnomAD4 genome

AF:

0.130

AC:

19782

AN:

152108

Hom.:

1643

Cov.:

AF XY:

0.132

AC XY:

9792

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.180

Gnomad4 AMR

AF:

0.121

Gnomad4 ASJ

AF:

0.134

Gnomad4 EAS

AF:

0.397

Gnomad4 SAS

AF:

0.140

Gnomad4 FIN

AF:

0.110

Gnomad4 NFE

AF:

0.0844

Gnomad4 OTH

AF:

0.127

Alfa

AF:

0.101

Hom.:

2156

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.11

T;.;T;.;.

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.83

T;.;.;T;T

MetaRNN

Benign

0.0047

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;L;L;L;.

MutationTaster

Benign

0.57

P;P;P;P

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.25

N;N;N;N;D

REVEL

Benign

0.094

Sift

Benign

0.17

T;T;T;T;T

Sift4G

Benign

0.70

T;T;T;T;.

Polyphen

0.0

B;B;B;B;.

Vest4

0.12

MPC

0.25

ClinPred

0.0078

GERP RS

3.2

Varity_R

0.058

gMVP

0.15

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