chr16-697333-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_153350.4(FBXL16):​c.73G>A​(p.Gly25Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

FBXL16
NM_153350.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.38
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.028312713).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FBXL16NM_153350.4 linkc.73G>A p.Gly25Ser missense_variant Exon 2 of 6 ENST00000397621.6 NP_699181.2 Q8N461-1
FBXL16XM_047433646.1 linkc.73G>A p.Gly25Ser 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.73G>A p.Gly25Ser missense_variant Exon 2 of 6 5 NM_153350.4 ENSP00000380746.1 Q8N461-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
39
GnomAD4 genome
Cov.:
31

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 06, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.73G>A (p.G25S) 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 73, causing the glycine (G) at amino acid position 25 to be replaced by a serine (S). 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
0.068
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
18
DANN
Benign
0.84
DEOGEN2
Benign
0.022
T;T
Eigen
Benign
-0.63
Eigen_PC
Benign
-0.48
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.76
.;T
M_CAP
Benign
0.039
D
MetaRNN
Benign
0.028
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.69
N;N
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
0.24
N;N
REVEL
Benign
0.076
Sift
Benign
0.92
T;T
Sift4G
Benign
0.68
T;T
Polyphen
0.0
B;B
Vest4
0.11
MutPred
0.17
Gain of phosphorylation at G25 (P = 0.0829);Gain of phosphorylation at G25 (P = 0.0829);
MVP
0.068
MPC
0.52
ClinPred
0.038
T
GERP RS
2.0
Varity_R
0.058
gMVP
0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-747333; API