chr12-1592914-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001405292.1(FBXL14):c.1152+1G>A variant causes a splice donor, intron change. The variant allele was found at a frequency of 0.0000312 in 1,603,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

FBXL14
NM_001405292.1 splice_donor, intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.13

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14305282).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001405292.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FBXL14	NM_152441.3	MANE Select	c.1153G>A	p.Val385Ile	missense	Exon 1 of 2	NP_689654.1	Q8N1E6
FBXL14	NM_001405291.1		c.1153G>A	p.Val385Ile	missense	Exon 1 of 2	NP_001392220.1
FBXL14	NM_001405292.1		c.1152+1G>A		splice_donor intron	N/A	NP_001392221.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FBXL14	ENST00000339235.4	TSL:1 MANE Select	c.1153G>A	p.Val385Ile	missense	Exon 1 of 2	ENSP00000344855.3	Q8N1E6
WNT5B	ENST00000969385.1		c.-134C>T		5_prime_UTR	Exon 1 of 5	ENSP00000639444.1
FBXL14	ENST00000923181.1		c.1152+1G>A		splice_donor intron	N/A	ENSP00000593240.1

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000855

AC:

AN:

245742

AF XY:

0.000113

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00200

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000262

AC:

AN:

1451636

Hom.:

Cov.:

AF XY:

0.0000278

AC XY:

AN XY:

720436

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33334

American (AMR)

AF:

0.00

AC:

AN:

44354

Ashkenazi Jewish (ASJ)

AF:

0.00137

AC:

AN:

25544

East Asian (EAS)

AF:

0.00

AC:

AN:

39476

South Asian (SAS)

AF:

0.00

AC:

AN:

84918

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52890

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1105494

Other (OTH)

AF:

0.0000167

AC:

AN:

59894

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41458

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00230

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5206

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000166

Hom.:

Bravo

AF:

0.0000491

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000659

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.037

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.0084

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.4

PhyloP100

6.1

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.51

REVEL

Benign

0.20

Sift

Benign

0.38

Sift4G

Benign

0.42

Polyphen

0.98

Vest4

0.55

MVP

0.73

MPC

1.0

ClinPred

0.14

GERP RS

5.0

Varity_R

0.16

gMVP

0.26

Mutation Taster

=35/65

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over