19-6466505-CTC-GTA

Variant names:

• chr19-6466505-CTC-GTA
• NM_139161.5:c.196_198delCTCinsGTA
• CRB3 p.Leu66Val

Variant summary

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

The NM_139161.5(CRB3):​c.196_198delCTCinsGTA​(p.Leu66Val) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. L66F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CRB3 NM_139161.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.39
• Publications: 0 publications found

Genes affected

CRB3 (HGNC:20237): (crumbs cell polarity complex component 3) This gene encodes a member of the Crumbs family of proteins. This gene is widely expressed in epithelial tissues where the encoded protein isoforms play various roles such as the control of cytokinesis and ciliogenesis or the formation of tight junctions. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139161.5. 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
	CRB3	NM_139161.5	MANE Select	c.196_198delCTCinsGTA	p.Leu66Val	missense	N/A	NP_631900.1	Q9BUF7-1
	CRB3	NM_174881.4		c.196_198delCTCinsGTA	p.Leu66Val	missense	N/A	NP_777377.1	Q9BUF7-2
	CRB3	NM_174882.3		c.196_198delCTCinsGTA	p.Leu66Val	missense	N/A	NP_777378.1	Q9BUF7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRB3	ENST00000600229.6	TSL:2 MANE Select	c.196_198delCTCinsGTA	p.Leu66Val	missense	N/A	ENSP00000472010.1	Q9BUF7-1
	CRB3	ENST00000356762.7	TSL:1	c.196_198delCTCinsGTA	p.Leu66Val	missense	N/A	ENSP00000349204.2	Q9BUF7-2
	CRB3	ENST00000308243.7	TSL:2	c.196_198delCTCinsGTA	p.Leu66Val	missense	N/A	ENSP00000310123.6	Q9BUF7-1

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		5.4

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: chr19-6466516;