chr12-48914428-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_033124.5(CCDC65):c.325G>T(p.Ala109Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,612,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A109V) has been classified as Uncertain significance.
Frequency
Consequence
NM_033124.5 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 |
---|---|---|---|---|---|---|---|
CCDC65 | NM_033124.5 | c.325G>T | p.Ala109Ser | missense_variant | 3/8 | ENST00000320516.5 | |
CCDC65 | NM_001286957.2 | c.-105G>T | 5_prime_UTR_variant | 3/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC65 | ENST00000320516.5 | c.325G>T | p.Ala109Ser | missense_variant | 3/8 | 1 | NM_033124.5 | P2 | |
CCDC65 | ENST00000266984.9 | c.325G>T | p.Ala109Ser | missense_variant | 3/9 | 5 | A2 | ||
CCDC65 | ENST00000552942.5 | c.301-3847G>T | intron_variant | 5 | |||||
CCDC65 | ENST00000547861.5 | c.*156G>T | 3_prime_UTR_variant, NMD_transcript_variant | 3/8 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152232Hom.: 0 Cov.: 31
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460526Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 726610
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152232Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1AN XY: 74362
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 27 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 04, 2021 | In summary, this variant is a novel missense change with uncertain impact on protein function. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a CCDC65-related disease. This sequence change replaces alanine with serine at codon 109 of the CCDC65 protein (p.Ala109Ser). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and serine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at