16-722784-T-C
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001378030.1(CCDC78):āc.1307A>Gā(p.Lys436Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,612,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_001378030.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CCDC78 | NM_001378030.1 | c.1307A>G | p.Lys436Arg | missense_variant | 14/14 | ENST00000345165.10 | NP_001364959.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CCDC78 | ENST00000345165.10 | c.1307A>G | p.Lys436Arg | missense_variant | 14/14 | 5 | NM_001378030.1 | ENSP00000316851.5 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152202Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000801 AC: 2AN: 249632Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135504
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1460364Hom.: 0 Cov.: 34 AF XY: 0.0000193 AC XY: 14AN XY: 726480
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152202Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74346
ClinVar
Submissions by phenotype
Congenital myopathy with internal nuclei and atypical cores Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 04, 2023 | This variant is present in population databases (rs748114954, gnomAD 0.003%). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. This variant has not been reported in the literature in individuals affected with CCDC78-related conditions. This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 435 of the CCDC78 protein (p.Ser435Gly). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at