rs750379614
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001378030.1(CCDC78):āc.356C>Gā(p.Pro119Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P119H) has been classified as Uncertain significance.
Frequency
Consequence
NM_001378030.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC78 | NM_001378030.1 | c.356C>G | p.Pro119Arg | missense_variant | 4/14 | ENST00000345165.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC78 | ENST00000345165.10 | c.356C>G | p.Pro119Arg | missense_variant | 4/14 | 5 | NM_001378030.1 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460318Hom.: 0 Cov.: 37 AF XY: 0.00000275 AC XY: 2AN XY: 726452
GnomAD4 genome ? Cov.: 34
ClinVar
Submissions by phenotype
Congenital myopathy with internal nuclei and atypical cores Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 01, 2017 | In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a CCDC78-related disease. This sequence change replaces proline with arginine at codon 119 of the CCDC78 protein (p.Pro119Arg). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and arginine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at