NM_001382779.1:c.152C>T

Variant names:

• chr16-30925906-C-T
• rs1189512553
• NM_001382779.1:c.152C>T

Variant summary

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

The NM_001382779.1(FBXL19):​c.152C>T​(p.Ser51Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000744 in 1,343,300 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S51S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: FBXL19 NM_001382779.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.90
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.152C>T	p.Ser51Leu	missense	Exon 2 of 11	NP_001369708.1	H3BPZ0
	FBXL19	NM_001282351.1		c.-727C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 11	NP_001269280.1	H3BVB1
	FBXL19	NM_001099784.3		c.212C>T	p.Ser71Leu	missense	Exon 2 of 11	NP_001093254.2	Q6PCT2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL19	ENST00000338343.10	TSL:5 MANE Select	c.152C>T	p.Ser51Leu	missense	Exon 2 of 11	ENSP00000339712.4	H3BPZ0
	FBXL19	ENST00000427128.5	TSL:1	c.14C>T	p.Ser5Leu	missense	Exon 1 of 10	ENSP00000397913.1	H7C112
	FBXL19	ENST00000471231.6	TSL:2	c.-727C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 11	ENSP00000458033.1	H3BVB1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000760 AC: 1 AN: 131598 AF XY: 0.0000140

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: 0.0000155

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.44e-7 AC: 1 AN: 1343300 Hom.: 0 Cov.: 30 AF XY: 0.00000152 AC XY: 1 AN XY: 660012

African (AFR) AF: 0.00 AC: 0 AN: 27332

American (AMR) AF: 0.00 AC: 0 AN: 25146

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19912

East Asian (EAS) AF: 0.00 AC: 0 AN: 33950

South Asian (SAS) AF: 0.00 AC: 0 AN: 67548

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49434

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5338

European-Non Finnish (NFE) AF: 9.44e-7 AC: 1 AN: 1059372

Other (OTH) AF: 0.00 AC: 0 AN: 55268

GnomAD4 genome Cov.: 32

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	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.68	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		7.9
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-5.7	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.71
MutPred		0.60		Gain of stability (P = 0.0333)
MVP		0.21
MPC		2.4
ClinPred		0.98	D
GERP RS		2.0
PromoterAI		0.0082	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.77
gMVP		0.89

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: rs1189512553; hg19: chr16-30937227;