rs60495385

Variant names:

• chr7-5500919-C-G
• rs60495385
• NM_024963.6:c.1350G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-5500919-C-G
• chr7-5500919-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024963.6(FBXL18):​c.1350G>C​(p.Lys450Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000268 in 1,567,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K450K) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: FBXL18 NM_024963.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.66
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13048062).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024963.6. 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
	FBXL18	NM_024963.6	MANE Select	c.1350G>C	p.Lys450Asn	missense	Exon 3 of 5	NP_079239.3
	FBXL18	NM_001321213.2		c.1350G>C	p.Lys450Asn	missense	Exon 3 of 5	NP_001308142.1	Q96ME1-5
	FBXL18	NM_001363441.2		c.1350G>C	p.Lys450Asn	missense	Exon 3 of 5	NP_001350370.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL18	ENST00000382368.8	TSL:5 MANE Select	c.1350G>C	p.Lys450Asn	missense	Exon 3 of 5	ENSP00000371805.3	Q96ME1-4
	FBXL18	ENST00000458142.1	TSL:2	c.999G>C	p.Lys333Asn	missense	Exon 1 of 3	ENSP00000405896.1	A0A994ENR3
	FBXL18	ENST00000948868.1		c.1131G>C	p.Lys377Asn	missense	Exon 2 of 4	ENSP00000618927.1

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000254 AC: 5 AN: 197166 AF XY: 0.0000184

Gnomad AFR exome AF: 0.000407

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 AF: 0.0000134 AC: 19 AN: 1415530 Hom.: 0 Cov.: 30 AF XY: 0.00000286 AC XY: 2 AN XY: 699878

African (AFR) AF: 0.000249 AC: 8 AN: 32110

American (AMR) AF: 0.00 AC: 0 AN: 36972

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23574

East Asian (EAS) AF: 0.00 AC: 0 AN: 39068

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 80254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5582

European-Non Finnish (NFE) AF: 9.18e-7 AC: 1 AN: 1089692

Other (OTH) AF: 0.000154 AC: 9 AN: 58256

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152226 Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11 AN XY: 74372

African (AFR) AF: 0.000555 AC: 23 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000418 Hom.: 0

Bravo AF: 0.000189

ExAC AF: 0.0000420 AC: 5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.076	T
Eigen	Benign	0.067
Eigen_PC	Benign	0.13
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.7
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.12
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.99	D
Vest4		0.34
MutPred		0.21		Loss of methylation at K450 (P = 0.0186)
MVP		0.70
MPC		1.5
ClinPred		0.19	T
GERP RS		4.5
gMVP		0.79
Mutation Taster		=64/36	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: rs60495385; hg19: chr7-5540550;