rs759937836
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_213607.3(CCDC103):āc.710A>Gā(p.Glu237Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,562,554 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 ā ). Synonymous variant affecting the same amino acid position (i.e. E237E) has been classified as Likely benign.
Frequency
Consequence
NM_213607.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC103 | NM_213607.3 | c.710A>G | p.Glu237Gly | missense_variant | 4/4 | ENST00000417826.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC103 | ENST00000417826.3 | c.710A>G | p.Glu237Gly | missense_variant | 4/4 | 1 | NM_213607.3 | P1 | |
CCDC103 | ENST00000410006.6 | c.710A>G | p.Glu237Gly | missense_variant | 4/4 | 2 | P1 | ||
CCDC103 | ENST00000357776.6 | c.710A>G | p.Glu237Gly | missense_variant | 4/4 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 151806Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000156 AC: 22AN: 1410748Hom.: 0 Cov.: 32 AF XY: 0.0000186 AC XY: 13AN XY: 697204
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 151806Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74140
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | UNC Molecular Genetics Laboratory, University of North Carolina at Chapel Hill | Nov 08, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 27, 2021 | This sequence change replaces glutamic acid with glycine at codon 237 of the CCDC103 protein (p.Glu237Gly). The glutamic acid residue is weakly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with CCDC103-related conditions. ClinVar contains an entry for this variant (Variation ID: 455030). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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