NM_001141947.3:c.79_81delCATinsTAC

Variant names:

• chr3-56559571-CAT-TAC
• NM_001141947.3:c.79_81delCATinsTAC
• CCDC66 p.His27Tyr

Variant summary

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

The NM_001141947.3(CCDC66):​c.79_81delCATinsTAC​(p.His27Tyr) variant causes a missense, splice region 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H27R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCDC66 NM_001141947.3 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.04
• Publications: 0 publications found

Genes affected

CCDC66 (HGNC:27709): (coiled-coil domain containing 66) Enables microtubule binding activity. Involved in cilium assembly; microtubule bundle formation; and regulation of protein localization to cilium. Located in several cellular components, including Flemming body; microtubule cytoskeleton; and photoreceptor inner segment. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001141947.3. 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
	CCDC66	NM_001141947.3	MANE Select	c.79_81delCATinsTAC	p.His27Tyr	missense splice_region	N/A	NP_001135419.1	A2RUB6-1
	CCDC66	NM_001353147.1		c.79_81delCATinsTAC	p.His27Tyr	missense splice_region	N/A	NP_001340076.1
	CCDC66	NM_001353148.1		c.79_81delCATinsTAC	p.His27Tyr	missense splice_region	N/A	NP_001340077.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC66	ENST00000394672.8	TSL:1 MANE Select	c.79_81delCATinsTAC	p.His27Tyr	missense splice_region	N/A	ENSP00000378167.3	A2RUB6-1
	CCDC66	ENST00000326595.11	TSL:1	c.-24_-22delCATinsTAC		splice_region	Exon 3 of 18	ENSP00000326050.7	A2RUB6-3
	CCDC66	ENST00000326595.11	TSL:1	c.-24_-22delCATinsTAC		5_prime_UTR	Exon 3 of 18	ENSP00000326050.7	A2RUB6-3

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.0

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: chr3-56593599;