rs749951287
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_001378030.1(CCDC78):āc.683A>Cā(p.Glu228Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,612,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_001378030.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CCDC78 | NM_001378030.1 | c.683A>C | p.Glu228Ala | missense_variant | 8/14 | ENST00000345165.10 | NP_001364959.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CCDC78 | ENST00000345165.10 | c.683A>C | p.Glu228Ala | missense_variant | 8/14 | 5 | NM_001378030.1 | ENSP00000316851 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152224Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000243 AC: 6AN: 247044Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134498
GnomAD4 exome AF: 0.0000253 AC: 37AN: 1459864Hom.: 0 Cov.: 37 AF XY: 0.0000248 AC XY: 18AN XY: 726190
GnomAD4 genome AF: 0.0000525 AC: 8AN: 152342Hom.: 0 Cov.: 34 AF XY: 0.0000806 AC XY: 6AN XY: 74484
ClinVar
Submissions by phenotype
Congenital myopathy with internal nuclei and atypical cores Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 20, 2024 | This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 228 of the CCDC78 protein (p.Glu228Ala). This variant is present in population databases (rs749951287, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with CCDC78-related conditions. ClinVar contains an entry for this variant (Variation ID: 566102). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CCDC78 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at