Variant 3-172251438-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_022763.4(FNDC3B):c.687T>C(p.His229His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0185 in 1,613,822 control chromosomes in the GnomAD database, including 1,184 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.054 ( 572 hom., cov: 31)

Exomes 𝑓: 0.015 ( 612 hom. )

Consequence

FNDC3B
NM_022763.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.41

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 3-172251438-T-C is Benign according to our data. Variant chr3-172251438-T-C is described in ClinVar as [Benign]. Clinvar id is 3056937.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.41 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 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.687T>C	p.His229His	synonymous_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.687T>C	p.His229His	synonymous_variant	6/26	1	NM_022763.4	ENSP00000411242.2		Q53EP0-1

Frequencies

GnomAD3 genomes

AF:

0.0541

AC:

8217

AN:

151888

Hom.:

571

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.0165

Gnomad AMR

AF:

0.0351

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00709

Gnomad FIN

AF:

0.00312

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0123

Gnomad OTH

AF:

0.0441

GnomAD3 exomes

AF:

0.0207

AC:

5201

AN:

250870

Hom.:

242

AF XY:

0.0186

AC XY:

2525

AN XY:

135582

show subpopulations

Gnomad AFR exome

AF:

0.153

Gnomad AMR exome

AF:

0.0192

Gnomad ASJ exome

AF:

0.0271

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00758

Gnomad FIN exome

AF:

0.00296

Gnomad NFE exome

AF:

0.0119

Gnomad OTH exome

AF:

0.0222

GnomAD4 exome

AF:

0.0147

AC:

21543

AN:

1461816

Hom.:

612

Cov.:

AF XY:

0.0142

AC XY:

10352

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.163

Gnomad4 AMR exome

AF:

0.0223

Gnomad4 ASJ exome

AF:

0.0254

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00743

Gnomad4 FIN exome

AF:

0.00318

Gnomad4 NFE exome

AF:

0.0108

Gnomad4 OTH exome

AF:

0.0234

GnomAD4 genome

AF:

0.0542

AC:

8243

AN:

152006

Hom.:

572

Cov.:

AF XY:

0.0524

AC XY:

3894

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.159

Gnomad4 AMR

AF:

0.0350

Gnomad4 ASJ

AF:

0.0285

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00730

Gnomad4 FIN

AF:

0.00312

Gnomad4 NFE

AF:

0.0123

Gnomad4 OTH

AF:

0.0436

Alfa

AF:

0.0364

Hom.:

152

Bravo

AF:

0.0619

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.0165

EpiControl

AF:

0.0156

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

Dec 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

-0.65

CADD

Benign

7.7

DANN

Benign

0.41

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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