12-67312684-CTG-TTA

Variant names:

• chr12-67312684-CTG-TTA
• NM_018448.5:c.3547_3549delCTGinsTTA
• CAND1 p.1184

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_018448.5(CAND1):​c.3547_3549delCTGinsTTA​(p.1184) variant causes a synonymous change involving the alteration of a 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. Synonymous variant affecting the same amino acid position (i.e. L1183L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CAND1 NM_018448.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.99
• Publications: 0 publications found

Genes affected

CAND1 (HGNC:30688): (cullin associated and neddylation dissociated 1) This gene encodes an essential regulator of Cullin-RING ubiquitin ligases, which are in involved in ubiquitinylation of proteins degraded by the Ub proteasome system. The encoded protein binds to unneddylated cullin-RING box protein complexes and acts as an inhibitor of cullin neddylation and of Skp1, cullin, and F box ubiquitin ligase complex assembly and activity. In mammalian cell culture, this protein predominantly localizes to the cytoplasm. Knockdown of this gene in preadipocytes results in blocked adipogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018448.5. 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
	CAND1	NM_018448.5	MANE Select	c.3547_3549delCTGinsTTA	p.1184	synonymous	N/A	NP_060918.2
	CAND1	NM_001329674.2		c.3475_3477delCTGinsTTA	p.1160	synonymous	N/A	NP_001316603.1
	CAND1	NM_001329675.2		c.3475_3477delCTGinsTTA	p.1160	synonymous	N/A	NP_001316604.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAND1	ENST00000545606.6	TSL:1 MANE Select	c.3547_3549delCTGinsTTA	p.1184	synonymous	N/A	ENSP00000442318.1	Q86VP6-1
	CAND1	ENST00000544619.1	TSL:1	c.2167_2169delCTGinsTTA	p.724	synonymous	N/A	ENSP00000444089.1	A0A0C4DGH5
	CAND1	ENST00000909423.1		c.3382_3384delCTGinsTTA	p.1129	synonymous	N/A	ENSP00000579482.1

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		8.0

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: chr12-67706464;