rs151189508
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_033124.5(CCDC65):āc.548T>Cā(p.Ile183Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000502 in 1,614,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I183M) has been classified as Likely benign.
Frequency
Consequence
NM_033124.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC65 | NM_033124.5 | c.548T>C | p.Ile183Thr | missense_variant | 4/8 | ENST00000320516.5 | |
CCDC65 | NM_001286957.2 | c.119T>C | p.Ile40Thr | missense_variant | 4/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC65 | ENST00000320516.5 | c.548T>C | p.Ile183Thr | missense_variant | 4/8 | 1 | NM_033124.5 | P2 | |
CCDC65 | ENST00000266984.9 | c.548T>C | p.Ile183Thr | missense_variant | 4/9 | 5 | A2 | ||
CCDC65 | ENST00000552942.5 | c.301-1228T>C | intron_variant | 5 | |||||
CCDC65 | ENST00000547861.5 | c.*379T>C | 3_prime_UTR_variant, NMD_transcript_variant | 4/8 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000315 AC: 48AN: 152140Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000235 AC: 59AN: 251450Hom.: 0 AF XY: 0.000265 AC XY: 36AN XY: 135902
GnomAD4 exome AF: 0.000522 AC: 763AN: 1461836Hom.: 0 Cov.: 32 AF XY: 0.000523 AC XY: 380AN XY: 727230
GnomAD4 genome ? AF: 0.000315 AC: 48AN: 152258Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23AN XY: 74472
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 27 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 2022 | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 183 of the CCDC65 protein (p.Ile183Thr). This variant is present in population databases (rs151189508, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with CCDC65-related conditions. ClinVar contains an entry for this variant (Variation ID: 241746). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine 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