rs920133176

Variant names:

• chr2-68464974-C-G
• rs920133176
• NM_001024680.3:c.172G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-68464974-C-G
• chr2-68464974-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001024680.3(FBXO48):​c.172G>C​(p.Ala58Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. A58T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FBXO48 NM_001024680.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.48

Genes affected

FBXO48 (HGNC:33857): (F-box protein 48) Predicted to be involved in SCF-dependent proteasomal ubiquitin-dependent protein catabolic process. Predicted to be part of SCF ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.98

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO48	NM_001024680.3	c.172G>C	p.Ala58Pro	missense_variant	Exon 3 of 4	ENST00000377957.4	NP_001019851.1
FBXO48	XM_005264407.4	c.172G>C	p.Ala58Pro	missense_variant	Exon 3 of 4		XP_005264464.1
FBXO48	XM_017004437.3	c.172G>C	p.Ala58Pro	missense_variant	Exon 3 of 4		XP_016859926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO48	ENST00000377957.4	c.172G>C	p.Ala58Pro	missense_variant	Exon 3 of 4	1	NM_001024680.3	ENSP00000367193.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.42	T
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.85	T
M_CAP	Uncertain	0.086	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Uncertain	0.25	D
MutationAssessor	Pathogenic	4.3	H
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.55
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.073	T
Polyphen		1.0	D
Vest4		0.94
MutPred		0.88		Loss of MoRF binding (P = 0.048);
MVP		0.63
MPC		0.77
ClinPred		1.0	D
GERP RS		6.1
Varity_R		0.90
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs920133176; hg19: chr2-68692106;