chr12-48904948-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_033124.5(CCDC65):c.135C>A(p.Asp45Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000558 in 1,596,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_033124.5 missense, splice_region
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 |
---|---|---|---|---|---|---|---|
CCDC65 | NM_033124.5 | c.135C>A | p.Asp45Glu | missense_variant, splice_region_variant | 2/8 | ENST00000320516.5 | |
CCDC65 | NM_001286957.2 | c.-279-16C>A | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC65 | ENST00000320516.5 | c.135C>A | p.Asp45Glu | missense_variant, splice_region_variant | 2/8 | 1 | NM_033124.5 | P2 | |
CCDC65 | ENST00000266984.9 | c.135C>A | p.Asp45Glu | missense_variant, splice_region_variant | 2/9 | 5 | A2 | ||
CCDC65 | ENST00000552942.5 | c.135C>A | p.Asp45Glu | missense_variant, splice_region_variant | 2/6 | 5 | |||
CCDC65 | ENST00000547861.5 | c.111-16C>A | splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000412 AC: 10AN: 242460Hom.: 0 AF XY: 0.0000611 AC XY: 8AN XY: 130936
GnomAD4 exome AF: 0.0000589 AC: 85AN: 1444144Hom.: 0 Cov.: 30 AF XY: 0.0000614 AC XY: 44AN XY: 716278
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74342
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 27 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 15, 2021 | 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 missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with CCDC65-related disease. This variant is present in population databases (rs184028693, ExAC 0.009%). This sequence change replaces aspartic acid with glutamic acid at codon 45 of the CCDC65 protein (p.Asp45Glu). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at