chr2-68464328-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001024680.3(FBXO48):​c.349G>T​(p.Glu117*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

FBXO48
NM_001024680.3 stop_gained

Scores

3
3
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.99
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FBXO48NM_001024680.3 linkc.349G>T p.Glu117* stop_gained Exon 4 of 4 ENST00000377957.4 NP_001019851.1 Q5FWF7
FBXO48XM_005264407.4 linkc.349G>T p.Glu117* stop_gained Exon 4 of 4 XP_005264464.1 Q5FWF7
FBXO48XM_017004437.3 linkc.349G>T p.Glu117* stop_gained Exon 4 of 4 XP_016859926.1 Q5FWF7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FBXO48ENST00000377957.4 linkc.349G>T p.Glu117* stop_gained Exon 4 of 4 1 NM_001024680.3 ENSP00000367193.2 Q5FWF7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000411
AC:
6
AN:
1461564
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727094
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.57
D
BayesDel_noAF
Pathogenic
0.59
CADD
Pathogenic
35
DANN
Uncertain
1.0
Eigen
Pathogenic
0.70
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Uncertain
0.95
D
Vest4
0.014
GERP RS
4.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.20
Details are displayed if max score is > 0.2
DS_AL_spliceai
0.20
Position offset: 42

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-68691460; API