22-38673201-CTG-GTT

Variant names:

• chr22-38673201-CTG-GTT
• NM_015373.4:c.346_348delCTGinsGTT
• CBY1 p.Leu116Val

Variant summary

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

The NM_015373.4(CBY1):​c.346_348delCTGinsGTT​(p.Leu116Val) variant causes a missense change. 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: CBY1 NM_015373.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.81
• Publications: 0 publications found

Genes affected

CBY1 (HGNC:1307): (chibby 1, beta catenin antagonist) Beta-catenin is a transcriptional activator and oncoprotein involved in the development of several cancers. The protein encoded by this gene interacts directly with the C-terminal region of beta-catenin, inhibiting oncogenic beta-catenin-mediated transcriptional activation by competing with transcription factors for binding to beta-catenin. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

TOMM22-DT (HGNC:56758): (TOMM22 divergent transcript)

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015373.4. 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
	CBY1	NM_015373.4	MANE Select	c.346_348delCTGinsGTT	p.Leu116Val	missense	N/A	NP_056188.1	Q9Y3M2
	CBY1	NM_001002880.4		c.346_348delCTGinsGTT	p.Leu116Val	missense	N/A	NP_001002880.3	Q9Y3M2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBY1	ENST00000216029.8	TSL:1 MANE Select	c.346_348delCTGinsGTT	p.Leu116Val	missense	N/A	ENSP00000216029.3	Q9Y3M2
	TOMM22-DT	ENST00000444381.1	TSL:1	n.96-1506_96-1504delCAGinsAAC		intron	N/A
	CBY1	ENST00000930725.1		c.355_357delCTGinsGTT	p.Leu119Val	missense	N/A	ENSP00000600784.1

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		4.8

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: chr22-39069206;