15-63597559-CC-TT

Variant names:

• chr15-63597559-CC-TT
• NM_001367807.1:c.167_168delCCinsTT
• FBXL22 p.Ser56Phe

Variant summary

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

The NM_001367807.1(FBXL22):​c.167_168delCCinsTT​(p.Ser56Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S56P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FBXL22 NM_001367807.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.09
• Publications: 0 publications found

Genes affected

FBXL22 (HGNC:27537): (F-box and leucine rich repeat protein 22) This gene encodes a member of the F-box protein family. This F-box protein interacts with S-phase kinase-associated protein 1A and cullin in order to form SCF complexes which function as ubiquitin ligases.[provided by RefSeq, Sep 2010]

USP3-AS1 (HGNC:44140): (USP3 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367807.1. 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
	FBXL22	NM_001367807.1	MANE Select	c.167_168delCCinsTT	p.Ser56Phe	missense	N/A	NP_001354736.1	A0A1W2PQW8
	FBXL22	NM_203373.3		c.167_168delCCinsTT	p.Ser56Phe	missense	N/A	NP_976307.2	Q6P050
	FBXL22	NM_001367808.1		c.167_168delCCinsTT	p.Ser56Phe	missense	N/A	NP_001354737.1	H0YMQ4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL22	ENST00000638704.2	TSL:2 MANE Select	c.167_168delCCinsTT	p.Ser56Phe	missense	N/A	ENSP00000492359.1	A0A1W2PQW8
	FBXL22	ENST00000360587.2	TSL:1	c.167_168delCCinsTT	p.Ser56Phe	missense	N/A	ENSP00000353794.3	Q6P050
	USP3-AS1	ENST00000558831.5	TSL:1	n.173-2774_173-2773delGGinsAA		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr15-63889758;