chr22-32475396-T-C

Variant names:

• chr22-32475396-T-C
• rs8137714
• NM_012179.4:c.122+272T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012179.4(FBXO7):​c.122+272T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FBXO7 NM_012179.4 intron
• Scores: Splicing: ADA: 0.00005583
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301
• Publications: 19 publications found

Genes affected

FBXO7 (HGNC:13586): (F-box protein 7) This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class and it may play a role in regulation of hematopoiesis. Alternatively spliced transcript variants of this gene have been identified with the full-length natures of only some variants being determined. [provided by RefSeq, Jul 2008]

FBXO7 Gene-Disease associations (from GenCC):

• parkinsonian-pyramidal syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037294954).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012179.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO7	NM_012179.4	MANE Select	c.122+272T>C		intron	N/A	NP_036311.3
	FBXO7	NM_001033024.2		c.35T>C	p.Leu12Pro	missense splice_region	Exon 1 of 9	NP_001028196.1
	FBXO7	NM_001257990.2		c.-223T>C		splice_region	Exon 1 of 9	NP_001244919.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO7	ENST00000266087.12	TSL:1 MANE Select	c.122+272T>C		intron	N/A	ENSP00000266087.7
	FBXO7	ENST00000452138.3	TSL:2	c.35T>C	p.Leu12Pro	missense splice_region	Exon 1 of 9	ENSP00000388547.2
	FBXO7	ENST00000397426.5	TSL:2	c.-223T>C		splice_region	Exon 1 of 9	ENSP00000380571.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.042
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	5.4
DANN	Benign	0.54
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0087	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.30
PROVEAN	Benign	0.79	N
REVEL	Benign	0.14
Sift	Benign	0.22	T
Sift4G	Benign	0.38	T
Polyphen		0.0	B
Vest4		0.040
MutPred		0.074		Loss of stability (P = 0.0383)
MVP		0.030
ClinPred		0.091	T
GERP RS		-6.1
PromoterAI		0.086	Neutral
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000056
dbscSNV1_RF	Benign	0.0
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: rs8137714; hg19: chr22-32871383;