15-63597513-G-T

Variant names:

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

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>T​(p.Asp41Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,122 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. 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: 𝑓 0.0000066 (0 hom., 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=0.1603713).

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>T	p.Asp41Tyr	missense	Exon 1 of 2	NP_001354736.1	A0A1W2PQW8
	FBXL22	NM_203373.3		c.121G>T	p.Asp41Tyr	missense	Exon 1 of 2	NP_976307.2	Q6P050
	FBXL22	NM_001367808.1		c.121G>T	p.Asp41Tyr	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>T	p.Asp41Tyr	missense	Exon 1 of 2	ENSP00000492359.1	A0A1W2PQW8
	FBXL22	ENST00000360587.2	TSL:1	c.121G>T	p.Asp41Tyr	missense	Exon 1 of 2	ENSP00000353794.3	Q6P050
	USP3-AS1	ENST00000558831.5	TSL:1	n.173-2727C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152122 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152122 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74304

African (AFR) AF: 0.0000241 AC: 1 AN: 41408

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.057	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.52	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.69	N
PhyloP100		3.8
PrimateAI	Benign	0.35	T
REVEL	Benign	0.15
Sift4G	Uncertain	0.0060	D
Vest4		0.22
MVP		0.40
MPC		0.77
ClinPred		0.77	D
GERP RS		4.5
PromoterAI		-0.036	Neutral
Varity_R		0.076
gMVP		0.33

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;