Variant chr3-48378467-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_207102.2(FBXW12):c.556A>G(p.Met186Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00444 in 1,614,102 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0042 ( 4 hom., cov: 30)

Exomes 𝑓: 0.0045 ( 23 hom. )

Consequence

FBXW12
NM_207102.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00300

Variant links:

Genes affected

FBXW12 (HGNC:20729): (F-box and WD repeat domain containing 12) Members of the F-box protein family, such as FBXW12, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (MIM 601434), cullin (see CUL1; MIM 603034), 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]

FBXW12 links:

FBXW12 (HGNC:):

FBXW12 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0056948066).

BP6

Variant 3-48378467-A-G is Benign according to our data. Variant chr3-48378467-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2653786.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXW12	NM_207102.2 linkuse as main transcript	c.556A>G	p.Met186Val	missense_variant	6/11	ENST00000296438.9	NP_996985.2	Q6X9E4-1
FBXW12	NM_001159929.1 linkuse as main transcript	c.499A>G	p.Met167Val	missense_variant	5/10		NP_001153401.1	Q6X9E4-3
FBXW12	NM_001159927.1 linkuse as main transcript	c.406-933A>G		intron_variant			NP_001153399.1	Q6X9E4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXW12	ENST00000296438.9 linkuse as main transcript	c.556A>G	p.Met186Val	missense_variant	6/11	1	NM_207102.2	ENSP00000296438.5		Q6X9E4-1

Frequencies

GnomAD3 genomes

AF:

0.00424

AC:

645

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.00531

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00830

Gnomad FIN

AF:

0.00434

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00523

Gnomad OTH

AF:

0.00575

GnomAD3 exomes

AF:

0.00522

AC:

1313

AN:

251374

Hom.:

AF XY:

0.00567

AC XY:

770

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.000861

Gnomad AMR exome

AF:

0.00347

Gnomad ASJ exome

AF:

0.0114

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00947

Gnomad FIN exome

AF:

0.00365

Gnomad NFE exome

AF:

0.00579

Gnomad OTH exome

AF:

0.00603

GnomAD4 exome

AF:

0.00446

AC:

6514

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00477

AC XY:

3469

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.00382

Gnomad4 ASJ exome

AF:

0.0108

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00880

Gnomad4 FIN exome

AF:

0.00346

Gnomad4 NFE exome

AF:

0.00425

Gnomad4 OTH exome

AF:

0.00528

GnomAD4 genome

AF:

0.00424

AC:

646

AN:

152232

Hom.:

Cov.:

AF XY:

0.00427

AC XY:

318

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00108

Gnomad4 AMR

AF:

0.00530

Gnomad4 ASJ

AF:

0.0124

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00851

Gnomad4 FIN

AF:

0.00434

Gnomad4 NFE

AF:

0.00523

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.00521

Hom.:

Bravo

AF:

0.00411

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00570

AC:

ExAC

AF:

0.00560

AC:

680

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00736

EpiControl

AF:

0.00818

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

FBXW12: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.074

DANN

Benign

0.37

DEOGEN2

Benign

0.0043

T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.42

T;T;T

MetaRNN

Benign

0.0057

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.036

Sift

Uncertain

0.0070

D;D;D

Sift4G

Uncertain

0.024

D;D;D

Polyphen

0.012

B;.;.

Vest4

0.17

MVP

0.39

MPC

0.090

ClinPred

0.0068

GERP RS

-5.7

Varity_R

0.23

gMVP

0.21

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