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GeneBe

3-172335000-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_022763.4(FNDC3B):c.1698G>A(p.Thr566=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00299 in 1,613,676 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0031 ( 6 hom. )

Consequence

FNDC3B
NM_022763.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.341
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-172335000-G-A is Benign according to our data. Variant chr3-172335000-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2654279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.341 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 349 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FNDC3BNM_022763.4 linkuse as main transcriptc.1698G>A p.Thr566= synonymous_variant 15/26 ENST00000415807.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FNDC3BENST00000415807.7 linkuse as main transcriptc.1698G>A p.Thr566= synonymous_variant 15/261 NM_022763.4 P1Q53EP0-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00230
AC:
349
AN:
152020
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000797
Gnomad AMI
AF:
0.0735
Gnomad AMR
AF:
0.000983
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000569
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00334
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.00190
AC:
478
AN:
251280
Hom.:
1
AF XY:
0.00184
AC XY:
250
AN XY:
135828
show subpopulations
Gnomad AFR exome
AF:
0.000615
Gnomad AMR exome
AF:
0.000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000693
Gnomad NFE exome
AF:
0.00383
Gnomad OTH exome
AF:
0.00130
GnomAD4 exome
AF:
0.00306
AC:
4470
AN:
1461544
Hom.:
6
Cov.:
31
AF XY:
0.00294
AC XY:
2138
AN XY:
727070
show subpopulations
Gnomad4 AFR exome
AF:
0.000568
Gnomad4 AMR exome
AF:
0.000179
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00114
Gnomad4 NFE exome
AF:
0.00381
Gnomad4 OTH exome
AF:
0.00242
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00229
AC:
349
AN:
152132
Hom.:
2
Cov.:
32
AF XY:
0.00206
AC XY:
153
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.000795
Gnomad4 AMR
AF:
0.000982
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000569
Gnomad4 NFE
AF:
0.00334
Gnomad4 OTH
AF:
0.000474
Alfa
AF:
0.00244
Hom.:
0
Bravo
AF:
0.00252
EpiCase
AF:
0.00295
EpiControl
AF:
0.00439

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

FNDC3B-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJan 21, 2020This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenDec 01, 2022FNDC3B: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.47
Cadd
Benign
2.0
Dann
Benign
0.86

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.

Other links and lift over

dbSNP: rs139505585; hg19: chr3-172052790; API