chr12-1592922-C-T

Variant names:

• chr12-1592922-C-T
• rs748877691
• NM_152441.3:c.1145G>A

Variant summary

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

The NM_152441.3(FBXL14):​c.1145G>A​(p.Cys382Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000193 in 1,454,098 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: FBXL14 NM_152441.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.04
• Publications: 1 publications found

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]

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]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152441.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL14	NM_152441.3	MANE Select	c.1145G>A	p.Cys382Tyr	missense	Exon 1 of 2	NP_689654.1	Q8N1E6
	FBXL14	NM_001405291.1		c.1145G>A	p.Cys382Tyr	missense	Exon 1 of 2	NP_001392220.1
	FBXL14	NM_001405292.1		c.1145G>A	p.Cys382Tyr	missense	Exon 1 of 2	NP_001392221.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL14	ENST00000339235.4	TSL:1 MANE Select	c.1145G>A	p.Cys382Tyr	missense	Exon 1 of 2	ENSP00000344855.3	Q8N1E6
	FBXL14	ENST00000923181.1		c.1145G>A	p.Cys382Tyr	missense	Exon 1 of 2	ENSP00000593240.1
	WNT5B	ENST00000969385.1		c.-126C>T		5_prime_UTR	Exon 1 of 5	ENSP00000639444.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000970 AC: 24 AN: 247544 AF XY: 0.0000449

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000699

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000193 AC: 28 AN: 1454098 Hom.: 0 Cov.: 31 AF XY: 0.0000111 AC XY: 8 AN XY: 722022

African (AFR) AF: 0.00 AC: 0 AN: 33358

American (AMR) AF: 0.000630 AC: 28 AN: 44438

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25762

East Asian (EAS) AF: 0.00 AC: 0 AN: 39512

South Asian (SAS) AF: 0.00 AC: 0 AN: 85390

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52920

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106984

Other (OTH) AF: 0.00 AC: 0 AN: 59988

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.6	L
PhyloP100		6.0
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.29
Sift	Benign	0.052	T
Sift4G	Benign	0.079	T
Polyphen		0.87	P
Vest4		0.86
MutPred		0.47		Loss of catalytic residue at P381 (P = 0.0094)
MVP		0.53
MPC		2.0
ClinPred		0.14	T
GERP RS		5.0
Varity_R		0.43
gMVP		0.75
Mutation Taster		=32/68	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs748877691; hg19: chr12-1702088;