Variant 3-172329051-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_022763.4(FNDC3B):c.1354G>T(p.Ala452Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,613,382 control chromosomes in the GnomAD database, including 162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.010 ( 17 hom., cov: 32)

Exomes 𝑓: 0.011 ( 145 hom. )

Consequence

FNDC3B
NM_022763.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.21

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01394847).

BP6

Variant 3-172329051-G-T is Benign according to our data. Variant chr3-172329051-G-T is described in ClinVar as [Benign]. Clinvar id is 3039307.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 1519 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FNDC3B	NM_022763.4 linkuse as main transcript	c.1354G>T	p.Ala452Ser	missense_variant	12/26	ENST00000415807.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FNDC3B	ENST00000415807.7 linkuse as main transcript	c.1354G>T	p.Ala452Ser	missense_variant	12/26	1	NM_022763.4	P1	Q53EP0-1

Frequencies

GnomAD3 genomes

AF:

0.00998

AC:

1519

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0113

Gnomad ASJ

AF:

0.0291

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.0101

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0147

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.0101

AC:

2532

AN:

250832

Hom.:

AF XY:

0.0101

AC XY:

1370

AN XY:

135590

show subpopulations

Gnomad AFR exome

AF:

0.00265

Gnomad AMR exome

AF:

0.00416

Gnomad ASJ exome

AF:

0.0360

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00331

Gnomad FIN exome

AF:

0.0108

Gnomad NFE exome

AF:

0.0139

Gnomad OTH exome

AF:

0.0126

GnomAD4 exome

AF:

0.0113

AC:

16446

AN:

1461128

Hom.:

145

Cov.:

AF XY:

0.0113

AC XY:

8201

AN XY:

726868

show subpopulations

Gnomad4 AFR exome

AF:

0.00209

Gnomad4 AMR exome

AF:

0.00439

Gnomad4 ASJ exome

AF:

0.0373

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00334

Gnomad4 FIN exome

AF:

0.0116

Gnomad4 NFE exome

AF:

0.0122

Gnomad4 OTH exome

AF:

0.0120

GnomAD4 genome

AF:

0.00998

AC:

1519

AN:

152254

Hom.:

Cov.:

AF XY:

0.00931

AC XY:

693

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00217

Gnomad4 AMR

AF:

0.0112

Gnomad4 ASJ

AF:

0.0291

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.0101

Gnomad4 NFE

AF:

0.0147

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.0140

Hom.:

Bravo

AF:

0.00934

TwinsUK

AF:

0.0113

AC:

ALSPAC

AF:

0.0117

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.0123

AC:

106

ExAC

AF:

0.00981

AC:

1191

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0140

EpiControl

AF:

0.0130

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

FNDC3B-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 08, 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

0.21

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.29

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.15

T;T;T

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.98

MetaRNN

Benign

0.014

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.7

L;L;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.18

Sift

Benign

0.28

T;T;T

Sift4G

Benign

0.13

T;T;T

Polyphen

0.24

B;B;B

Vest4

0.69

MPC

0.31

ClinPred

0.046

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.53

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