NM_032447.5:c.7830G>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032447.5(FBN3):c.7830G>T(p.Glu2610Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 1,613,530 control chromosomes in the GnomAD database, including 254,989 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 (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.63 ( 32164 hom., cov: 32)

Exomes 𝑓: 0.55 ( 222825 hom. )

Consequence

FBN3
NM_032447.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.13

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.964196E-6).

BP6

Variant 19-8073170-C-A is Benign according to our data. Variant chr19-8073170-C-A is described in ClinVar as [Benign]. Clinvar id is 1669122.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-8073170-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN3	NM_032447.5 link	c.7830G>T	p.Glu2610Asp	missense_variant	Exon 62 of 64	ENST00000600128.6	NP_115823.3	Q75N90A8KAY2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FBN3	ENST00000600128.6 link	c.7830G>T	p.Glu2610Asp	missense_variant	Exon 62 of 64	1	NM_032447.5	ENSP00000470498.1	Q75N90
FBN3	ENST00000270509.6 link	c.7830G>T	p.Glu2610Asp	missense_variant	Exon 61 of 63	1		ENSP00000270509.2	Q75N90
FBN3	ENST00000601739.5 link	c.7830G>T	p.Glu2610Asp	missense_variant	Exon 62 of 64	1		ENSP00000472324.1	Q75N90
FBN3	ENST00000651877.1 link	c.7956G>T	p.Glu2652Asp	missense_variant	Exon 62 of 64			ENSP00000498507.1	A0A494C0D8

Frequencies

GnomAD3 genomes

AF:

0.633

AC:

96149

AN:

151890

Hom.:

32116

Cov.:

show subpopulations

Gnomad AFR

AF:

0.855

Gnomad AMI

AF:

0.630

Gnomad AMR

AF:

0.619

Gnomad ASJ

AF:

0.422

Gnomad EAS

AF:

0.378

Gnomad SAS

AF:

0.394

Gnomad FIN

AF:

0.589

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.557

Gnomad OTH

AF:

0.609

GnomAD3 exomes

AF:

0.543

AC:

135728

AN:

250018

Hom.:

38610

AF XY:

0.531

AC XY:

71883

AN XY:

135430

show subpopulations

Gnomad AFR exome

AF:

0.862

Gnomad AMR exome

AF:

0.590

Gnomad ASJ exome

AF:

0.423

Gnomad EAS exome

AF:

0.384

Gnomad SAS exome

AF:

0.390

Gnomad FIN exome

AF:

0.594

Gnomad NFE exome

AF:

0.552

Gnomad OTH exome

AF:

0.536

GnomAD4 exome

AF:

0.547

AC:

799403

AN:

1461522

Hom.:

222825

Cov.:

AF XY:

0.541

AC XY:

393470

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.863

Gnomad4 AMR exome

AF:

0.598

Gnomad4 ASJ exome

AF:

0.423

Gnomad4 EAS exome

AF:

0.399

Gnomad4 SAS exome

AF:

0.395

Gnomad4 FIN exome

AF:

0.591

Gnomad4 NFE exome

AF:

0.554

Gnomad4 OTH exome

AF:

0.538

GnomAD4 genome

AF:

0.633

AC:

96263

AN:

152008

Hom.:

32164

Cov.:

AF XY:

0.630

AC XY:

46800

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.854

Gnomad4 AMR

AF:

0.619

Gnomad4 ASJ

AF:

0.422

Gnomad4 EAS

AF:

0.379

Gnomad4 SAS

AF:

0.393

Gnomad4 FIN

AF:

0.589

Gnomad4 NFE

AF:

0.557

Gnomad4 OTH

AF:

0.610

Alfa

AF:

0.555

Hom.:

48136

Bravo

AF:

0.646

TwinsUK

AF:

0.558

AC:

2070

ALSPAC

AF:

0.532

AC:

2052

ESP6500AA

AF:

0.845

AC:

3725

ESP6500EA

AF:

0.540

AC:

4648

ExAC

AF:

0.546

AC:

66232

Asia WGS

AF:

0.446

AC:

1551

AN:

3478

EpiCase

AF:

0.539

EpiControl

AF:

0.536

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

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

0.026

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.0050

DANN

Benign

0.14

DEOGEN2

Benign

0.015

T;T;T

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.51

.;.;T

MetaRNN

Benign

0.0000020

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-2.7

N;N;N

PrimateAI

Uncertain

0.67

PROVEAN

Benign

2.4

.;N;.

REVEL

Benign

0.18

Sift

Benign

1.0

.;T;.

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.13

MutPred

0.41

Loss of catalytic residue at E2610 (P = 0.2439);Loss of catalytic residue at E2610 (P = 0.2439);Loss of catalytic residue at E2610 (P = 0.2439);

MPC

0.17

ClinPred

0.0087

GERP RS

-3.8

Varity_R

0.075

gMVP

0.74

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