Variant 12-1593686-G-A 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_152441.3(FBXL14):c.381C>T(p.Cys127=) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00726 in 1,614,158 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0052 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0075 ( 53 hom. )

Consequence

FBXL14
NM_152441.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.87

Variant links:

Genes affected

FBXL14 (HGNC:28624): (F-box and leucine rich repeat protein 14) Members of the F-box protein family, such as FBXL14, 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]

FBXL14 links:

WNT5B (HGNC:16265): (Wnt family member 5B) The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It encodes a protein which shows 94% and 80% amino acid identity to the mouse Wnt5b protein and the human WNT5A protein, respectively. Alternative splicing of this gene generates 2 transcript variants. [provided by RefSeq, Jul 2008]

WNT5B 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 (BayesDel_noAF=-0.55).

BP6

Variant 12-1593686-G-A is Benign according to our data. Variant chr12-1593686-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2642570.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBXL14	NM_152441.3 linkuse as main transcript	c.381C>T	p.Cys127=	synonymous_variant	1/2	ENST00000339235.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
FBXL14	ENST00000339235.4 linkuse as main transcript	c.381C>T	p.Cys127=	synonymous_variant	1/2	1	NM_152441.3	P1
WNT5B	ENST00000537031.5 linkuse as main transcript	c.-58+18845G>A		intron_variant		2		P1
WNT5B	ENST00000539198.5 linkuse as main transcript	c.-57-37612G>A		intron_variant		4
WNT5B	ENST00000545811.5 linkuse as main transcript	c.-57-37612G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00520

AC:

791

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0140

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00816

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00483

AC:

1214

AN:

251122

Hom.:

AF XY:

0.00487

AC XY:

661

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.000636

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0126

Gnomad NFE exome

AF:

0.00766

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.00748

AC:

10932

AN:

1461810

Hom.:

Cov.:

AF XY:

0.00735

AC XY:

5347

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.000671

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.0122

Gnomad4 NFE exome

AF:

0.00893

Gnomad4 OTH exome

AF:

0.00470

GnomAD4 genome

AF:

0.00519

AC:

791

AN:

152348

Hom.:

Cov.:

AF XY:

0.00549

AC XY:

409

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00152

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0140

Gnomad4 NFE

AF:

0.00816

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00629

Hom.:

Bravo

AF:

0.00402

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00649

EpiControl

AF:

0.00610

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

Jan 01, 2023

FBXL14: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.97

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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