chr16-697333-C-T

Variant names:

• chr16-697333-C-T
• NM_153350.4:c.73G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.38

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]

ACMG classification

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
FBXL16	NM_153350.4	c.73G>A	p.Gly25Ser	missense_variant	Exon 2 of 6	ENST00000397621.6	NP_699181.2
FBXL16	XM_047433646.1	c.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
FBXL16	ENST00000397621.6	c.73G>A	p.Gly25Ser	missense_variant	Exon 2 of 6	5	NM_153350.4	ENSP00000380746.1

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

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;