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GeneBe

3-172251438-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_022763.4(FNDC3B):c.687T>C(p.His229=) 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 (★).

Frequency

Genomes: 𝑓 0.054 ( 572 hom., cov: 31)
Exomes 𝑓: 0.015 ( 612 hom. )

Consequence

FNDC3B
NM_022763.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter 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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 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=-0.65).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-172251438-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 criteria_provided_single_submitter, 1 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=1.41 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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 UniProt
FNDC3BNM_022763.4 linkuse as main transcriptc.687T>C p.His229= synonymous_variant 6/26 ENST00000415807.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FNDC3BENST00000415807.7 linkuse as main transcriptc.687T>C p.His229= synonymous_variant 6/261 NM_022763.4 P1Q53EP0-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0541
AC:
8217
AN:
151888
Hom.:
571
Cov.:
31
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.:
32
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0542
AC:
8243
AN:
152006
Hom.:
572
Cov.:
31
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:
67
AN:
3478
EpiCase
AF:
0.0165
EpiControl
AF:
0.0156

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 submitterclinical testingPreventionGenetics, part of Exact SciencesDec 11, 2019This 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.

Other links and lift over

dbSNP: rs35366330; hg19: chr3-171969228; API