16-30927883-C-G

Variant names:

• chr16-30927883-C-G
• rs770363065
• NM_001382779.1:c.547C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001382779.1(FBXL19):​c.547C>G​(p.Pro183Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000148 in 1,350,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P183S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: FBXL19 NM_001382779.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.674
• Publications: 0 publications found

Genes affected

FBXL19 (HGNC:25300): (F-box and leucine rich repeat protein 19) This gene encodes a member of the Skp1-Cullin-F-box family of E3 ubiquitin ligases. The encoded protein is reported to bind to the transmembrane receptor interleukin 1 receptor-like 1 and regulate its ubiquitination and degradation. This protein has been linked to the regulation of pulmonary inflammation and psoriasis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05836782).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382779.1. 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
	FBXL19	NM_001382779.1	MANE Select	c.547C>G	p.Pro183Ala	missense	Exon 5 of 11	NP_001369708.1	H3BPZ0
	FBXL19	NM_001099784.3		c.607C>G	p.Pro203Ala	missense	Exon 5 of 11	NP_001093254.2	Q6PCT2-1
	FBXL19	NM_001382780.1		c.613C>G	p.Pro205Ala	missense	Exon 5 of 11	NP_001369709.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL19	ENST00000338343.10	TSL:5 MANE Select	c.547C>G	p.Pro183Ala	missense	Exon 5 of 11	ENSP00000339712.4	H3BPZ0
	FBXL19	ENST00000427128.5	TSL:1	c.409C>G	p.Pro137Ala	missense	Exon 4 of 10	ENSP00000397913.1	H7C112
	FBXL19	ENST00000562319.7	TSL:2	c.607C>G	p.Pro203Ala	missense	Exon 5 of 11	ENSP00000455529.2	Q6PCT2-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000902 AC: 1 AN: 110882 AF XY: 0.0000166

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000225

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000148 AC: 2 AN: 1350230 Hom.: 0 Cov.: 33 AF XY: 0.00000300 AC XY: 2 AN XY: 665800

African (AFR) AF: 0.00 AC: 0 AN: 29654

American (AMR) AF: 0.00 AC: 0 AN: 27710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23272

East Asian (EAS) AF: 0.00 AC: 0 AN: 35478

South Asian (SAS) AF: 0.00 AC: 0 AN: 74742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46898

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5102

European-Non Finnish (NFE) AF: 9.51e-7 AC: 1 AN: 1051344

Other (OTH) AF: 0.0000178 AC: 1 AN: 56030

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000268 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	12
DANN	Benign	0.52
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.67
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.043
Sift	Benign	0.40	T
Sift4G	Benign	0.15	T
Polyphen		0.0	B
Vest4		0.24
MutPred		0.26		Loss of glycosylation at P203 (P = 0.0372)
MVP		0.043
MPC		0.020
ClinPred		0.040	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.054
gMVP		0.23

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: rs770363065; hg19: chr16-30939204;