16-697387-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_153350.4(FBXL16):​c.19G>A​(p.Asp7Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 1,535,494 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

FBXL16
NM_153350.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.219
Variant links:
Genes affected
FBXL16 (HGNC:14150): (F-box and leucine rich repeat protein 16) Members of the F-box protein family, such as FBXL16, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (MIM 601434), cullin (see CUL1; MIM 603134), and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (Jin et al., 2004 [PubMed 15520277]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.010226548).
BS2
High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FBXL16NM_153350.4 linkc.19G>A p.Asp7Asn missense_variant Exon 2 of 6 ENST00000397621.6 NP_699181.2 Q8N461-1
FBXL16XM_047433646.1 linkc.19G>A p.Asp7Asn missense_variant Exon 2 of 6 XP_047289602.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FBXL16ENST00000397621.6 linkc.19G>A p.Asp7Asn missense_variant Exon 2 of 6 5 NM_153350.4 ENSP00000380746.1 Q8N461-1

Frequencies

GnomAD3 genomes
AF:
0.0000724
AC:
11
AN:
152036
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00104
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000219
AC:
29
AN:
132542
Hom.:
0
AF XY:
0.000304
AC XY:
22
AN XY:
72270
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000410
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00117
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000387
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000134
AC:
186
AN:
1383340
Hom.:
1
Cov.:
39
AF XY:
0.000158
AC XY:
108
AN XY:
682768
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000280
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000986
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000973
Gnomad4 OTH exome
AF:
0.0000346
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152154
Hom.:
0
Cov.:
31
AF XY:
0.0000672
AC XY:
5
AN XY:
74398
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000105
Hom.:
0
Bravo
AF:
0.0000416
ExAC
AF:
0.0000739
AC:
7

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 29, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.19G>A (p.D7N) alteration is located in exon 2 (coding exon 1) of the FBXL16 gene. This alteration results from a G to A substitution at nucleotide position 19, causing the aspartic acid (D) at amino acid position 7 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.076
BayesDel_addAF
Benign
-0.59
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
7.8
DANN
Benign
0.93
DEOGEN2
Benign
0.018
T;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-0.96
FATHMM_MKL
Benign
0.22
N
LIST_S2
Benign
0.61
.;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.010
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.34
N;N
PrimateAI
Benign
0.46
T
PROVEAN
Benign
0.35
N;N
REVEL
Benign
0.11
Sift
Benign
0.75
T;T
Sift4G
Benign
0.72
T;T
Polyphen
0.0
B;B
Vest4
0.084
MutPred
0.12
Gain of methylation at K11 (P = 0.1624);Gain of methylation at K11 (P = 0.1624);
MVP
0.068
MPC
0.51
ClinPred
0.021
T
GERP RS
-0.030
Varity_R
0.040
gMVP
0.12

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: rs770390917; hg19: chr16-747387; COSMIC: COSV60965228; COSMIC: COSV60965228; API