16-30927943-C-T

Variant names:

• chr16-30927943-C-T
• rs369148968
• NM_001382779.1:c.607C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001382779.1(FBXL19):​c.607C>T​(p.Pro203Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000218 in 1,377,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. P203A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: FBXL19 NM_001382779.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.36
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09849116).

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.607C>T	p.Pro203Ser	missense	Exon 5 of 11	NP_001369708.1	H3BPZ0
	FBXL19	NM_001099784.3		c.667C>T	p.Pro223Ser	missense	Exon 5 of 11	NP_001093254.2	Q6PCT2-1
	FBXL19	NM_001382780.1		c.673C>T	p.Pro225Ser	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.607C>T	p.Pro203Ser	missense	Exon 5 of 11	ENSP00000339712.4	H3BPZ0
	FBXL19	ENST00000427128.5	TSL:1	c.469C>T	p.Pro157Ser	missense	Exon 4 of 10	ENSP00000397913.1	H7C112
	FBXL19	ENST00000562319.7	TSL:2	c.667C>T	p.Pro223Ser	missense	Exon 5 of 11	ENSP00000455529.2	Q6PCT2-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000676 AC: 1 AN: 147836 AF XY: 0.00

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: 0.0000145

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000218 AC: 3 AN: 1377538 Hom.: 0 Cov.: 33 AF XY: 0.00000147 AC XY: 1 AN XY: 679478

African (AFR) AF: 0.00 AC: 0 AN: 30172

American (AMR) AF: 0.00 AC: 0 AN: 27744

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21250

East Asian (EAS) AF: 0.00 AC: 0 AN: 38156

South Asian (SAS) AF: 0.00 AC: 0 AN: 71684

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47872

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5424

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1078544

Other (OTH) AF: 0.00 AC: 0 AN: 56692

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000841 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.0013
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.26	N
PhyloP100		2.4
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.11
Sift	Benign	0.13	T
Sift4G	Benign	0.28	T
Polyphen		0.35	B
Vest4		0.26
MutPred		0.22		Gain of phosphorylation at P223 (P = 0.0085)
MVP		0.043
MPC		0.14
ClinPred		0.25	T
GERP RS		4.8
Varity_R		0.12
gMVP		0.24
Mutation Taster		=281/19	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: rs369148968; hg19: chr16-30939264;