12-1593686-G-A

Variant names:

• chr12-1593686-G-A
• rs150585689
• NM_152441.3:c.381C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_152441.3(FBXL14):​c.381C>T​(p.Cys127Cys) 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.87
• 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: Benign. The variant received -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 VariationId is 2642570.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.381C>T	p.Cys127Cys	synonymous	Exon 1 of 2	NP_689654.1	Q8N1E6
	FBXL14	NM_001405291.1		c.381C>T	p.Cys127Cys	synonymous	Exon 1 of 2	NP_001392220.1
	FBXL14	NM_001405292.1		c.381C>T	p.Cys127Cys	synonymous	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.381C>T	p.Cys127Cys	synonymous	Exon 1 of 2	ENSP00000344855.3	Q8N1E6
	FBXL14	ENST00000923181.1		c.381C>T	p.Cys127Cys	synonymous	Exon 1 of 2	ENSP00000593240.1
	WNT5B	ENST00000537031.5	TSL:2	c.-58+18845G>A		intron	N/A	ENSP00000439312.1	Q9H1J7

Frequencies

GnomAD3 genomes AF: 0.00520 AC: 791 AN: 152230 Hom.: 2 Cov.: 32

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

GnomAD2 exomes AF: 0.00483 AC: 1214 AN: 251122 AF XY: 0.00487

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 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.: 53 Cov.: 32 AF XY: 0.00735 AC XY: 5347 AN XY: 727204

African (AFR) AF: 0.00102 AC: 34 AN: 33480

American (AMR) AF: 0.000671 AC: 30 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86254

European-Finnish (FIN) AF: 0.0122 AC: 651 AN: 53356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00893 AC: 9928 AN: 1112000

Other (OTH) AF: 0.00470 AC: 284 AN: 60394

GnomAD4 genome AF: 0.00519 AC: 791 AN: 152348 Hom.: 2 Cov.: 32 AF XY: 0.00549 AC XY: 409 AN XY: 74502

African (AFR) AF: 0.00152 AC: 63 AN: 41584

American (AMR) AF: 0.00105 AC: 16 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.0140 AC: 149 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00816 AC: 555 AN: 68024

Other (OTH) AF: 0.00379 AC: 8 AN: 2110

Alfa AF: 0.00629 Hom.: 2

Bravo AF: 0.00402

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00649

EpiControl AF: 0.00610

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	11
DANN	Benign	0.97
PhyloP100		7.9
Mutation Taster		=19/81	disease causing

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

Other links and lift over

dbSNP: rs150585689; hg19: chr12-1702852;