9-37518257-G-C

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_012166.3(FBXO10):ā€‹c.2382C>Gā€‹(p.Leu794=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,614,072 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0060 ( 8 hom., cov: 33)
Exomes š‘“: 0.00059 ( 9 hom. )

Consequence

FBXO10
NM_012166.3 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: 0.0320
Variant links:
Genes affected
FBXO10 (HGNC:13589): (F-box protein 10) Members of the F-box protein family, such as FBXO10, 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 (Jin et al., 2004 [PubMed 15520277]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
Variant 9-37518257-G-C is Benign according to our data. Variant chr9-37518257-G-C is described in ClinVar as [Benign]. Clinvar id is 786908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.032 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00601 (915/152364) while in subpopulation AFR AF= 0.0211 (876/41588). AF 95% confidence interval is 0.0199. There are 8 homozygotes in gnomad4. There are 425 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FBXO10NM_012166.3 linkuse as main transcriptc.2382C>G p.Leu794= synonymous_variant 9/11 ENST00000432825.7 NP_036298.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FBXO10ENST00000432825.7 linkuse as main transcriptc.2382C>G p.Leu794= synonymous_variant 9/111 NM_012166.3 ENSP00000403802 P1Q9UK96-1
FBXO10ENST00000276960.7 linkuse as main transcriptc.*589C>G 3_prime_UTR_variant, NMD_transcript_variant 8/95 ENSP00000276960

Frequencies

GnomAD3 genomes
AF:
0.00600
AC:
914
AN:
152246
Hom.:
8
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0211
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00157
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:
0.0000147
Gnomad OTH
AF:
0.00669
GnomAD3 exomes
AF:
0.00138
AC:
345
AN:
249296
Hom.:
2
AF XY:
0.00105
AC XY:
142
AN XY:
135242
show subpopulations
Gnomad AFR exome
AF:
0.0209
Gnomad AMR exome
AF:
0.000434
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000354
Gnomad OTH exome
AF:
0.000496
GnomAD4 exome
AF:
0.000593
AC:
867
AN:
1461708
Hom.:
9
Cov.:
32
AF XY:
0.000507
AC XY:
369
AN XY:
727136
show subpopulations
Gnomad4 AFR exome
AF:
0.0219
Gnomad4 AMR exome
AF:
0.000514
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.00147
GnomAD4 genome
AF:
0.00601
AC:
915
AN:
152364
Hom.:
8
Cov.:
33
AF XY:
0.00570
AC XY:
425
AN XY:
74512
show subpopulations
Gnomad4 AFR
AF:
0.0211
Gnomad4 AMR
AF:
0.00157
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00662
Alfa
AF:
0.00192
Hom.:
0
Bravo
AF:
0.00682
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJul 04, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.33
CADD
Benign
7.5
DANN
Benign
0.72

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: rs76495281; hg19: chr9-37518254; API