5-108224214-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001163315.3(FBXL17):c.1521A>G(p.Ser507=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,597,460 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0069 (21 hom., cov: 32)
  • Exomes 𝑓: 0.00088 (21 hom.)
• Consequence: FBXL17 NM_001163315.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.38

Genes affected

FBXL17 (HGNC:13615): (F-box and leucine rich repeat protein 17) Members of the F-box protein family, such as FBXL17, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (MIM 601434), cullin (see CUL1; MIM 603134), and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (Jin et al., 2004 [PubMed 15520277]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 5-108224214-T-C is Benign according to our data. Variant chr5-108224214-T-C is described in ClinVar as [Benign]. Clinvar id is 775223.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.38 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00687 (1047/152306) while in subpopulation AFR AF= 0.0234 (974/41556). AF 95% confidence interval is 0.0222. There are 21 homozygotes in gnomad4. There are 509 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1029 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBXL17	NM_001163315.3	c.1521A>G	p.Ser507=	synonymous_variant	5/9	ENST00000542267.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBXL17	ENST00000542267.7	c.1521A>G	p.Ser507=	synonymous_variant	5/9	1	NM_001163315.3	P1
FBXL17	ENST00000496714.2	c.531A>G	p.Ser177=	synonymous_variant	4/7	1
FBXL17	ENST00000481160.1	n.177A>G		non_coding_transcript_exon_variant	3/5	3

Frequencies

GnomAD3 genomes AF: 0.00676 AC: 1029 AN: 152188 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.0231

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00525

GnomAD3 exomes AF: 0.00204 AC: 502 AN: 245628 Hom.: 9 AF XY: 0.00164 AC XY: 218 AN XY: 132836

Gnomad AFR exome AF: 0.0240

Gnomad AMR exome AF: 0.00188

Gnomad ASJ exome AF: 0.000302

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000374

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000269

Gnomad OTH exome AF: 0.00219

GnomAD4 exome AF: 0.000880 AC: 1272 AN: 1445154 Hom.: 21 Cov.: 25 AF XY: 0.000778 AC XY: 560 AN XY: 719506

Gnomad4 AFR exome AF: 0.0235

Gnomad4 AMR exome AF: 0.00222

Gnomad4 ASJ exome AF: 0.000346

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.000296

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000154

Gnomad4 OTH exome AF: 0.00242

GnomAD4 genome AF: 0.00687 AC: 1047 AN: 152306 Hom.: 21 Cov.: 32 AF XY: 0.00683 AC XY: 509 AN XY: 74486

Gnomad4 AFR AF: 0.0234

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00329 Hom.: 2

Bravo AF: 0.00780

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.54
Dann	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs112049764; hg19: chr5-107559915;