15-63597513-G-C

Variant names:

• chr15-63597513-G-C
• rs745537862
• NM_001367807.1:c.121G>C

Variant summary

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

The NM_001367807.1(FBXL22):​c.121G>C​(p.Asp41His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. D41N) 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: 3.79
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16733405).

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.121G>C	p.Asp41His	missense	Exon 1 of 2	NP_001354736.1	A0A1W2PQW8
	FBXL22	NM_203373.3		c.121G>C	p.Asp41His	missense	Exon 1 of 2	NP_976307.2	Q6P050
	FBXL22	NM_001367808.1		c.121G>C	p.Asp41His	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.121G>C	p.Asp41His	missense	Exon 1 of 2	ENSP00000492359.1	A0A1W2PQW8
	FBXL22	ENST00000360587.2	TSL:1	c.121G>C	p.Asp41His	missense	Exon 1 of 2	ENSP00000353794.3	Q6P050
	USP3-AS1	ENST00000558831.5	TSL:1	n.173-2727C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.053	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.55	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.69	N
PhyloP100		3.8
PrimateAI	Benign	0.34	T
REVEL	Benign	0.13
Sift4G	Uncertain	0.012	D
Vest4		0.17
MVP		0.32
MPC		0.75
ClinPred		0.76	D
GERP RS		4.5
PromoterAI		-0.24	Neutral
Varity_R		0.058
gMVP		0.25

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: rs745537862; hg19: chr15-63889712;