chr16-697387-C-T

Variant names:

• chr16-697387-C-T
• rs770390917
• NM_153350.4:c.19G>A

Variant summary

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

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. 17/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.219
• 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=0.010226548).
• BS2: High AC in GnomAd4 at 11 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.19G>A	p.Asp7Asn	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.19G>A	p.Asp7Asn	missense	Exon 2 of 6	ENSP00000380746.1	Q8N461-1
	FBXL16	ENST00000926353.1		c.19G>A	p.Asp7Asn	missense	Exon 2 of 6	ENSP00000596412.1
	FBXL16	ENST00000926354.1		c.19G>A	p.Asp7Asn	missense	Exon 2 of 6	ENSP00000596413.1

Frequencies

GnomAD3 genomes AF: 0.0000724 AC: 11 AN: 152036 Hom.: 0 Cov.: 31

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

GnomAD2 exomes AF: 0.000219 AC: 29 AN: 132542 AF XY: 0.000304

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 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

African (AFR) AF: 0.00 AC: 0 AN: 31538

American (AMR) AF: 0.0000280 AC: 1 AN: 35724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25076

East Asian (EAS) AF: 0.00 AC: 0 AN: 35688

South Asian (SAS) AF: 0.000986 AC: 78 AN: 79126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5604

European-Non Finnish (NFE) AF: 0.0000973 AC: 105 AN: 1079116

Other (OTH) AF: 0.0000346 AC: 2 AN: 57868

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152154 Hom.: 0 Cov.: 31 AF XY: 0.0000672 AC XY: 5 AN XY: 74398

African (AFR) AF: 0.0000482 AC: 2 AN: 41522

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67986

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000105 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.0000739 AC: 7

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	0.076
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.8
DANN	Benign	0.93
DEOGEN2	Benign	0.018	T
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
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		0.22
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.35	N
REVEL	Benign	0.11
Sift	Benign	0.75	T
Sift4G	Benign	0.72	T
Polyphen		0.0	B
Vest4		0.084
MutPred		0.12		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
Mutation Taster		=97/3	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: rs770390917; hg19: chr16-747387; COSMIC: COSV60965228; COSMIC: COSV60965228;