Variant 9-37531993-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_012166.3(FBXO10):c.1485C>T(p.Gly495=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00266 in 1,613,944 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 58 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 48 hom. )

Consequence

FBXO10
NM_012166.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.21

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]

FBXO10 links:

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=-0.59).

BP6

Variant 9-37531993-G-A is Benign according to our data. Variant chr9-37531993-G-A is described in ClinVar as [Benign]. Clinvar id is 785286.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.21 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0138 (2103/152290) while in subpopulation AFR AF= 0.0459 (1906/41546). AF 95% confidence interval is 0.0442. There are 58 homozygotes in gnomad4. There are 1047 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 58 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXO10	NM_012166.3 linkuse as main transcript	c.1485C>T	p.Gly495=	synonymous_variant	4/11	ENST00000432825.7	NP_036298.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXO10	ENST00000432825.7 linkuse as main transcript	c.1485C>T	p.Gly495=	synonymous_variant	4/11	1	NM_012166.3	ENSP00000403802	P1	Q9UK96-1
FBXO10	ENST00000543968.5 linkuse as main transcript	n.137C>T		non_coding_transcript_exon_variant	2/6	3
FBXO10	ENST00000276960.7 linkuse as main transcript	c.1485C>T	p.Gly495=	synonymous_variant, NMD_transcript_variant	4/9	5		ENSP00000276960

Frequencies

GnomAD3 genomes

AF:

0.0138

AC:

2105

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0460

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00963

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00363

AC:

905

AN:

249236

Hom.:

AF XY:

0.00262

AC XY:

354

AN XY:

135226

show subpopulations

Gnomad AFR exome

AF:

0.0471

Gnomad AMR exome

AF:

0.00298

Gnomad ASJ exome

AF:

0.00338

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000221

Gnomad OTH exome

AF:

0.00165

GnomAD4 exome

AF:

0.00150

AC:

2195

AN:

1461654

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

941

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.0472

Gnomad4 AMR exome

AF:

0.00324

Gnomad4 ASJ exome

AF:

0.00371

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000111

Gnomad4 OTH exome

AF:

0.00349

GnomAD4 genome

AF:

0.0138

AC:

2103

AN:

152290

Hom.:

Cov.:

AF XY:

0.0141

AC XY:

1047

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0459

Gnomad4 AMR

AF:

0.00961

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00604

Hom.:

Bravo

AF:

0.0163

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000415

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 submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

3.5

DANN

Benign

0.93

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over