16-724753-CC-AA

Variant names:

• chr16-724753-CC-AA
• NM_001378030.1:c.692_693delGGinsTT
• CCDC78 p.Arg231Leu

Variant summary

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

The NM_001378030.1(CCDC78):​c.692_693delGGinsTT​(p.Arg231Leu) 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 Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R231W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: CCDC78 NM_001378030.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.544
• Publications: 0 publications found

Genes affected

CCDC78 (HGNC:14153): (coiled-coil domain containing 78) Involved in de novo centriole assembly involved in multi-ciliated epithelial cell differentiation and skeletal muscle contraction. Located in several cellular components, including centriole; deuterosome; and sarcolemma. Implicated in centronuclear myopathy 4. [provided by Alliance of Genome Resources, Apr 2022]

CCDC78 Gene-Disease associations (from GenCC):

• congenital myopathy with internal nuclei and atypical cores

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• centronuclear myopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378030.1. 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
	CCDC78	NM_001378030.1	MANE Select	c.692_693delGGinsTT	p.Arg231Leu	missense	N/A	NP_001364959.1	H3BLT8
	CCDC78	NM_001031737.3		c.692_693delGGinsTT	p.Arg231Leu	missense	N/A	NP_001026907.2	A2IDD5-1
	CCDC78	NM_001378031.1		c.692_693delGGinsTT	p.Arg231Leu	missense	N/A	NP_001364960.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC78	ENST00000345165.10	TSL:5 MANE Select	c.692_693delGGinsTT	p.Arg231Leu	missense	N/A	ENSP00000316851.5	H3BLT8
	CCDC78	ENST00000293889.10	TSL:1	c.692_693delGGinsTT	p.Arg231Leu	missense	N/A	ENSP00000293889.6	A2IDD5-1
	CCDC78	ENST00000947033.1		c.692_693delGGinsTT	p.Arg231Leu	missense	N/A	ENSP00000617092.1

Frequencies

GnomAD3 genomes Cov.: 34

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

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.54

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: chr16-774753;