3-48373610-CA-AG

Variant names:

• chr3-48373610-CA-AG
• NM_207102.2:c.191_192delCAinsAG
• FBXW12 p.Thr64Lys

Variant summary

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

The NM_207102.2(FBXW12):​c.191_192delCAinsAG​(p.Thr64Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FBXW12 NM_207102.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140
• Publications: 0 publications found

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]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207102.2. 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
	FBXW12	NM_207102.2	MANE Select	c.191_192delCAinsAG	p.Thr64Lys	missense	N/A	NP_996985.2	Q6X9E4-1
	FBXW12	NM_001159929.1		c.134_135delCAinsAG	p.Thr45Lys	missense	N/A	NP_001153401.1	Q6X9E4-3
	FBXW12	NM_001159927.1		c.191_192delCAinsAG	p.Thr64Lys	missense	N/A	NP_001153399.1	Q6X9E4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXW12	ENST00000296438.9	TSL:1 MANE Select	c.191_192delCAinsAG	p.Thr64Lys	missense	N/A	ENSP00000296438.5	Q6X9E4-1
	FBXW12	ENST00000445170.5	TSL:1	c.134_135delCAinsAG	p.Thr45Lys	missense	N/A	ENSP00000406139.1	Q6X9E4-3
	FBXW12	ENST00000415155.5	TSL:1	c.191_192delCAinsAG	p.Thr64Lys	missense	N/A	ENSP00000414683.1	Q6X9E4-2

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.14

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-48415100;