7-5500980-G-C

Variant names:

• chr7-5500980-G-C
• rs763290880
• NM_024963.6:c.1289C>G

Variant summary

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

The NM_024963.6(FBXL18):​c.1289C>G​(p.Pro430Arg) 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. 14/20 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. P430L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FBXL18 NM_024963.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.83
• Publications: 0 publications found

Genes affected

FBXL18 (HGNC:21874): (F-box and leucine rich repeat protein 18) The protein encoded by this gene is a member of a family of proteins that contain an approximately 40-amino acid F-box motif. This motif is important for interaction with SKP1 and for targeting some proteins for degradation. The encoded protein has been shown to control the cellular level of FBXL7, a protein that induces mitotic arrest, by targeting it for polyubiquitylation and proteasomal degradation. Members of the F-box protein family, such as FBXL18, are characterized by an approximately 40-amino acid F-box motif. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains. [provided by RefSeq, Mar 2016]

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=0.19808367).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXL18	NM_024963.6	c.1289C>G	p.Pro430Arg	missense_variant	Exon 3 of 5	ENST00000382368.8	NP_079239.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXL18	ENST00000382368.8	c.1289C>G	p.Pro430Arg	missense_variant	Exon 3 of 5	5	NM_024963.6	ENSP00000371805.3
FBXL18	ENST00000458142.1	c.938C>G	p.Pro313Arg	missense_variant	Exon 1 of 3	2		ENSP00000405896.1
FBXL18	ENST00000415009.5	n.1289C>G		non_coding_transcript_exon_variant	Exon 3 of 7	2		ENSP00000415064.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 173402 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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Benign	0.96
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.8
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.14
Sift	Benign	0.20	T
Sift4G	Benign	0.10	T
Polyphen		0.52	P
Vest4		0.14
MutPred		0.23		Loss of loop (P = 0.0031);
MVP		0.68
MPC		0.66
ClinPred		0.39	T
GERP RS		4.5
gMVP		0.22
Mutation Taster		=89/11	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: rs763290880; hg19: chr7-5540611;