Variant 19-8066143-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_032447.5(FBN3):c.8206C>T(p.Arg2736Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000998 in 1,613,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

FBN3
NM_032447.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.90

Variant links:

Genes affected

FBN3 (HGNC:18794): (fibrillin 3) This gene encodes a memebr of the fibrillin protein family. Fibrillins are extracellular matrix molecules that assemble into microfibrils in many connective tissues. This gene is most highly expressed in fetal tissues and its protein product is localized to extracellular microfibrils of developing skeletal elements, skin, lung, kidney, and skeletal muscle. This gene is potentially involved in Weill-Marchesani syndrome. [provided by RefSeq, Mar 2016]

FBN3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01177752).

BP6

Variant 19-8066143-G-A is Benign according to our data. Variant chr19-8066143-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1103972.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBN3	NM_032447.5 linkuse as main transcript	c.8206C>T	p.Arg2736Trp	missense_variant	64/64	ENST00000600128.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
FBN3	ENST00000600128.6 linkuse as main transcript	c.8206C>T	p.Arg2736Trp	missense_variant	64/64	1	NM_032447.5
FBN3	ENST00000270509.6 linkuse as main transcript	c.8206C>T	p.Arg2736Trp	missense_variant	63/63	1
FBN3	ENST00000601739.5 linkuse as main transcript	c.8206C>T	p.Arg2736Trp	missense_variant	64/64	1
FBN3	ENST00000651877.1 linkuse as main transcript	c.8332C>T	p.Arg2778Trp	missense_variant	64/64			P1

Frequencies

GnomAD3 genomes

AF:

0.000512

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00176

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000157

AC:

AN:

248274

Hom.:

AF XY:

0.000141

AC XY:

AN XY:

134788

show subpopulations

Gnomad AFR exome

AF:

0.00181

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000270

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000568

AC:

AN:

1461146

Hom.:

Cov.:

AF XY:

0.0000468

AC XY:

AN XY:

726884

show subpopulations

Gnomad4 AFR exome

AF:

0.00170

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.000512

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00176

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000837

Hom.:

Bravo

AF:

0.000533

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000222

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Nov 30, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.13

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.17

T;T;T

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.52

FATHMM_MKL

Uncertain

0.92

M_CAP

Benign

0.077

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Benign

-0.32

MutationAssessor

Benign

2.0

M;M;M

MutationTaster

Benign

0.78

PrimateAI

Benign

0.20

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

0.13

B;B;B

Vest4

0.20

MVP

0.81

MPC

0.20

ClinPred

0.082

GERP RS

1.0

Varity_R

0.22

gMVP

0.57

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