16-697165-C-G

Variant names:

• chr16-697165-C-G
• rs202093624
• NM_153350.4:c.241G>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_153350.4(FBXL16):​c.241G>C​(p.Ala81Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000165 in 1,579,068 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00017 (1 hom.)
• Consequence: FBXL16 NM_153350.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.650
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.023083925).
• BS2: High AC in GnomAd4 at 24 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153350.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL16	NM_153350.4	MANE Select	c.241G>C	p.Ala81Pro	missense	Exon 2 of 6	NP_699181.2	Q8N461-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL16	ENST00000397621.6	TSL:5 MANE Select	c.241G>C	p.Ala81Pro	missense	Exon 2 of 6	ENSP00000380746.1	Q8N461-1
	FBXL16	ENST00000926353.1		c.241G>C	p.Ala81Pro	missense	Exon 2 of 6	ENSP00000596412.1
	FBXL16	ENST00000926354.1		c.241G>C	p.Ala81Pro	missense	Exon 2 of 6	ENSP00000596413.1

Frequencies

GnomAD3 genomes AF: 0.000159 AC: 24 AN: 151156 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000660

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000287

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000280

Gnomad OTH AF: 0.000481

GnomAD2 exomes AF: 0.000222 AC: 46 AN: 207002 AF XY: 0.000166

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000127

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00134

Gnomad NFE exome AF: 0.000236

Gnomad OTH exome AF: 0.000195

GnomAD4 exome AF: 0.000166 AC: 237 AN: 1427792 Hom.: 1 Cov.: 56 AF XY: 0.000157 AC XY: 111 AN XY: 707964

African (AFR) AF: 0.00 AC: 0 AN: 32788

American (AMR) AF: 0.000166 AC: 7 AN: 42136

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24462

East Asian (EAS) AF: 0.00 AC: 0 AN: 39368

South Asian (SAS) AF: 0.00 AC: 0 AN: 82080

European-Finnish (FIN) AF: 0.00118 AC: 53 AN: 45100

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5322

European-Non Finnish (NFE) AF: 0.000149 AC: 163 AN: 1097584

Other (OTH) AF: 0.000237 AC: 14 AN: 58952

GnomAD4 genome AF: 0.000159 AC: 24 AN: 151276 Hom.: 0 Cov.: 30 AF XY: 0.000122 AC XY: 9 AN XY: 73912

African (AFR) AF: 0.00 AC: 0 AN: 41252

American (AMR) AF: 0.0000659 AC: 1 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5038

South Asian (SAS) AF: 0.00 AC: 0 AN: 4796

European-Finnish (FIN) AF: 0.000287 AC: 3 AN: 10444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000280 AC: 19 AN: 67812

Other (OTH) AF: 0.000476 AC: 1 AN: 2102

Alfa AF: 0.000472 Hom.: 0

Bravo AF: 0.0000982

ExAC AF: 0.000188 AC: 22

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.44	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.65
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.17
Sift	Benign	0.076	T
Sift4G	Uncertain	0.049	D
Polyphen		0.0	B
Vest4		0.14
MVP		0.043
MPC		0.68
ClinPred		0.023	T
GERP RS		3.0
Varity_R		0.14
gMVP		0.24
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs202093624; hg19: chr16-747165;