Variant 3-172307438-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_022763.4(FNDC3B):c.1137C>T(p.Pro379=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,614,030 control chromosomes in the GnomAD database, including 151 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0088 ( 8 hom., cov: 32)

Exomes 𝑓: 0.012 ( 143 hom. )

Consequence

FNDC3B
NM_022763.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.59

Variant links:

Genes affected

FNDC3B (HGNC:24670): (fibronectin type III domain containing 3B) Enables RNA binding activity. Predicted to act upstream of or within several processes, including negative regulation of osteoblast differentiation; substrate adhesion-dependent cell spreading; and type II pneumocyte differentiation. Predicted to be located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

FNDC3B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 3-172307438-C-T is Benign according to our data. Variant chr3-172307438-C-T is described in ClinVar as [Benign]. Clinvar id is 773705.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd at 1336 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FNDC3B	NM_022763.4 linkuse as main transcript	c.1137C>T	p.Pro379=	synonymous_variant	10/26	ENST00000415807.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FNDC3B	ENST00000415807.7 linkuse as main transcript	c.1137C>T	p.Pro379=	synonymous_variant	10/26	1	NM_022763.4	P1	Q53EP0-1

Frequencies

GnomAD3 genomes

AF:

0.00878

AC:

1336

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00890

Gnomad FIN

AF:

0.0188

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0133

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00900

AC:

2264

AN:

251442

Hom.:

AF XY:

0.00959

AC XY:

1303

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.0145

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00967

Gnomad FIN exome

AF:

0.0180

Gnomad NFE exome

AF:

0.0115

Gnomad OTH exome

AF:

0.00766

GnomAD4 exome

AF:

0.0124

AC:

18064

AN:

1461764

Hom.:

143

Cov.:

AF XY:

0.0122

AC XY:

8900

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.00161

Gnomad4 AMR exome

AF:

0.00188

Gnomad4 ASJ exome

AF:

0.0127

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00988

Gnomad4 FIN exome

AF:

0.0180

Gnomad4 NFE exome

AF:

0.0136

Gnomad4 OTH exome

AF:

0.00949

GnomAD4 genome

AF:

0.00877

AC:

1336

AN:

152266

Hom.:

Cov.:

AF XY:

0.00892

AC XY:

664

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00200

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.0135

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00912

Gnomad4 FIN

AF:

0.0188

Gnomad4 NFE

AF:

0.0133

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.0110

Hom.:

Bravo

AF:

0.00689

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0106

EpiControl

AF:

0.0105

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jun 26, 2018	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	FNDC3B: BP4, BP7, BS1, BS2 -

FNDC3B-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 11, 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

BayesDel_noAF

Benign

-0.67

Cadd

Benign

3.7

Dann

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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