15-63597666-C-T

Variant names:

• chr15-63597666-C-T
• rs775494411
• NM_001367807.1:c.274C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001367807.1(FBXL22):​c.274C>T​(p.Leu92Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. L92H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FBXL22 NM_001367807.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.44
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3459007).

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.274C>T	p.Leu92Phe	missense	Exon 1 of 2	NP_001354736.1	A0A1W2PQW8
	FBXL22	NM_203373.3		c.274C>T	p.Leu92Phe	missense	Exon 1 of 2	NP_976307.2	Q6P050
	FBXL22	NM_001367808.1		c.274C>T	p.Leu92Phe	missense	Exon 1 of 2	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.274C>T	p.Leu92Phe	missense	Exon 1 of 2	ENSP00000492359.1	A0A1W2PQW8
	FBXL22	ENST00000360587.2	TSL:1	c.274C>T	p.Leu92Phe	missense	Exon 1 of 2	ENSP00000353794.3	Q6P050
	USP3-AS1	ENST00000558831.5	TSL:1	n.173-2880G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000806 AC: 2 AN: 248176 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

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: 0.00000138 AC: 2 AN: 1453526 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 721548

African (AFR) AF: 0.00 AC: 0 AN: 33340

American (AMR) AF: 0.0000448 AC: 2 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39476

South Asian (SAS) AF: 0.00 AC: 0 AN: 86142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106204

Other (OTH) AF: 0.00 AC: 0 AN: 59958

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.55	N
PhyloP100		2.4
PrimateAI	Uncertain	0.50	T
REVEL	Benign	0.10
Sift4G	Uncertain	0.034	D
Vest4		0.32
MVP		0.59
MPC		0.73
ClinPred		0.74	D
GERP RS		4.7
PromoterAI		0.019	Neutral
Varity_R		0.10
gMVP		0.24

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: rs775494411; hg19: chr15-63889865;