Variant 3-172251287-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_022763.4(FNDC3B):c.536C>G(p.Thr179Ser) variant causes a missense change. The variant allele was found at a frequency of 0.524 in 1,609,202 control chromosomes in the GnomAD database, including 226,650 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 0.61 ( 29755 hom., cov: 30)

Exomes 𝑓: 0.52 ( 196895 hom. )

Consequence

FNDC3B
NM_022763.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.11

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:

FNDC3B (HGNC:):

FNDC3B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.4724999E-6).

BP6

Variant 3-172251287-C-G is Benign according to our data. Variant chr3-172251287-C-G is described in ClinVar as [Benign]. Clinvar id is 3060403.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FNDC3B	NM_022763.4 linkuse as main transcript	c.536C>G	p.Thr179Ser	missense_variant	6/26	ENST00000415807.7	NP_073600.3	Q53EP0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FNDC3B	ENST00000415807.7 linkuse as main transcript	c.536C>G	p.Thr179Ser	missense_variant	6/26	1	NM_022763.4	ENSP00000411242.2		Q53EP0-1

Frequencies

GnomAD3 genomes

AF:

0.606

AC:

91957

AN:

151812

Hom.:

29701

Cov.:

show subpopulations

Gnomad AFR

AF:

0.857

Gnomad AMI

AF:

0.562

Gnomad AMR

AF:

0.532

Gnomad ASJ

AF:

0.509

Gnomad EAS

AF:

0.499

Gnomad SAS

AF:

0.561

Gnomad FIN

AF:

0.530

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.500

Gnomad OTH

AF:

0.559

GnomAD3 exomes

AF:

0.542

AC:

135829

AN:

250802

Hom.:

37953

AF XY:

0.534

AC XY:

72427

AN XY:

135600

show subpopulations

Gnomad AFR exome

AF:

0.867

Gnomad AMR exome

AF:

0.534

Gnomad ASJ exome

AF:

0.498

Gnomad EAS exome

AF:

0.512

Gnomad SAS exome

AF:

0.575

Gnomad FIN exome

AF:

0.520

Gnomad NFE exome

AF:

0.502

Gnomad OTH exome

AF:

0.516

GnomAD4 exome

AF:

0.516

AC:

751299

AN:

1457272

Hom.:

196895

Cov.:

AF XY:

0.515

AC XY:

373649

AN XY:

725152

show subpopulations

Gnomad4 AFR exome

AF:

0.871

Gnomad4 AMR exome

AF:

0.533

Gnomad4 ASJ exome

AF:

0.495

Gnomad4 EAS exome

AF:

0.434

Gnomad4 SAS exome

AF:

0.572

Gnomad4 FIN exome

AF:

0.514

Gnomad4 NFE exome

AF:

0.503

Gnomad4 OTH exome

AF:

0.529

GnomAD4 genome

AF:

0.606

AC:

92070

AN:

151930

Hom.:

29755

Cov.:

AF XY:

0.606

AC XY:

44998

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.857

Gnomad4 AMR

AF:

0.532

Gnomad4 ASJ

AF:

0.509

Gnomad4 EAS

AF:

0.498

Gnomad4 SAS

AF:

0.561

Gnomad4 FIN

AF:

0.530

Gnomad4 NFE

AF:

0.500

Gnomad4 OTH

AF:

0.559

Alfa

AF:

0.514

Hom.:

15489

Bravo

AF:

0.616

TwinsUK

AF:

0.501

AC:

1857

ALSPAC

AF:

0.514

AC:

1981

ESP6500AA

AF:

0.853

AC:

3758

ESP6500EA

AF:

0.493

AC:

4236

ExAC

AF:

0.550

AC:

66822

Asia WGS

AF:

0.575

AC:

1999

AN:

3478

EpiCase

AF:

0.483

EpiControl

AF:

0.486

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

FNDC3B-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 29, 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

0.16

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.035

T;T;T;T

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.39

.;.;T;T

MetaRNN

Benign

0.0000035

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.1

N;N;N;.

PrimateAI

Uncertain

0.62

PROVEAN

Benign

0.55

N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.76

T;T;T;T

Sift4G

Benign

0.82

T;T;T;T

Polyphen

0.0

B;B;B;.

Vest4

0.020

MutPred

0.26

Gain of disorder (P = 0.0581);Gain of disorder (P = 0.0581);Gain of disorder (P = 0.0581);.;

MPC

0.25

ClinPred

0.014

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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