chr3-196569017-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001105573.2(FBXO45):​c.33C>T​(p.Ala11Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0036 in 1,013,250 control chromosomes in the GnomAD database, including 122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0097 ( 55 hom., cov: 32)
Exomes 𝑓: 0.0026 ( 67 hom. )

Consequence

FBXO45
NM_001105573.2 synonymous

Scores

1
1

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.679
Variant links:
Genes affected
FBXO45 (HGNC:29148): (F-box protein 45) Members of the F-box protein family, such as FBXO45, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (MIM 601434), cullin (see CUL1; MIM 603134), and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (summary by Jin et al., 2004 [PubMed 15520277]).[supplied by OMIM, Jan 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 3-196569017-C-T is Benign according to our data. Variant chr3-196569017-C-T is described in ClinVar as [Benign]. Clinvar id is 773676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.679 with no splicing effect.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0582 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FBXO45NM_001105573.2 linkc.33C>T p.Ala11Ala synonymous_variant Exon 1 of 3 ENST00000311630.7 NP_001099043.1 P0C2W1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FBXO45ENST00000311630.7 linkc.33C>T p.Ala11Ala synonymous_variant Exon 1 of 3 1 NM_001105573.2 ENSP00000310332.6 P0C2W1
FBXO45ENST00000440469.1 linkc.-220+230C>T intron_variant Intron 1 of 2 2 ENSP00000389868.1 C9JLC0

Frequencies

GnomAD3 genomes
AF:
0.00964
AC:
1424
AN:
147774
Hom.:
52
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00152
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0475
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0453
Gnomad SAS
AF:
0.0640
Gnomad FIN
AF:
0.000224
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00137
Gnomad OTH
AF:
0.0108
GnomAD4 exome
AF:
0.00256
AC:
2215
AN:
865368
Hom.:
67
Cov.:
30
AF XY:
0.00263
AC XY:
1062
AN XY:
403622
show subpopulations
Gnomad4 AFR exome
AF:
0.000976
Gnomad4 AMR exome
AF:
0.0819
Gnomad4 ASJ exome
AF:
0.000172
Gnomad4 EAS exome
AF:
0.0468
Gnomad4 SAS exome
AF:
0.0510
Gnomad4 FIN exome
AF:
0.000267
Gnomad4 NFE exome
AF:
0.000835
Gnomad4 OTH exome
AF:
0.00843
GnomAD4 genome
AF:
0.00968
AC:
1432
AN:
147882
Hom.:
55
Cov.:
32
AF XY:
0.0109
AC XY:
784
AN XY:
72040
show subpopulations
Gnomad4 AFR
AF:
0.00151
Gnomad4 AMR
AF:
0.0480
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0453
Gnomad4 SAS
AF:
0.0641
Gnomad4 FIN
AF:
0.000224
Gnomad4 NFE
AF:
0.00137
Gnomad4 OTH
AF:
0.0106
Alfa
AF:
0.00572
Hom.:
1
Bravo
AF:
0.0127
Asia WGS
AF:
0.0340
AC:
103
AN:
3050

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.49
CADD
Benign
13
DANN
Uncertain
0.98

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs576470291; hg19: chr3-196295888; API