chr16-30928605-G-A

Variant names:

• chr16-30928605-G-A
• NM_001382779.1:c.766G>A

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.766G>A​(p.Gly256Arg) 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. 13/22 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: FBXL19 NM_001382779.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.47
• 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=0.22552136).

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.766G>A	p.Gly256Arg	missense	Exon 6 of 11	NP_001369708.1	H3BPZ0
	FBXL19	NM_001099784.3		c.826G>A	p.Gly276Arg	missense	Exon 6 of 11	NP_001093254.2	Q6PCT2-1
	FBXL19	NM_001282351.1		c.-113G>A		5_prime_UTR	Exon 6 of 11	NP_001269280.1	H3BVB1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL19	ENST00000338343.10	TSL:5 MANE Select	c.766G>A	p.Gly256Arg	missense	Exon 6 of 11	ENSP00000339712.4	H3BPZ0
	FBXL19	ENST00000427128.5	TSL:1	c.522+106G>A		intron	N/A	ENSP00000397913.1	H7C112
	FBXL19	ENST00000562319.7	TSL:2	c.826G>A	p.Gly276Arg	missense	Exon 6 of 11	ENSP00000455529.2	Q6PCT2-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

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	0.29
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.0052	T
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.55	N
PhyloP100		2.5
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.087
Sift	Benign	0.095	T
Sift4G	Benign	0.56	T
Polyphen		0.84	P
Vest4		0.51
MutPred		0.22		Gain of solvent accessibility (P = 0.0037)
MVP		0.043
MPC		0.021
ClinPred		0.45	T
GERP RS		5.2
Varity_R		0.12
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

hg19: chr16-30939926;