rs142180051
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The ENST00000293889.10(CCDC78):c.1277C>T(p.Thr426Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,612,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
ENST00000293889.10 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC78 | NM_001378030.1 | c.1281C>T | p.Tyr427= | synonymous_variant | 13/14 | ENST00000345165.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC78 | ENST00000345165.10 | c.1281C>T | p.Tyr427= | synonymous_variant | 13/14 | 5 | NM_001378030.1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152212Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000241 AC: 6AN: 249404Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135434
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1459918Hom.: 0 Cov.: 34 AF XY: 0.0000179 AC XY: 13AN XY: 726266
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152212Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2AN XY: 74356
ClinVar
Submissions by phenotype
Congenital myopathy with internal nuclei and atypical cores Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 14, 2024 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 426 of the CCDC78 protein (p.Thr426Met). This variant is present in population databases (rs142180051, gnomAD 0.02%). 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: 573114). 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | CCDC78: BP4 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at