rs1060503167
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_033124.5(CCDC65):c.1370_1371delTT(p.Phe457fs) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000396 in 1,614,178 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000040 ( 1 hom. )
Consequence
CCDC65
NM_033124.5 frameshift
NM_033124.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.92
Genes affected
CCDC65 (HGNC:29937): (coiled-coil domain containing 65) This gene encodes a sperm tail protein that is highly expressed in adult testis, spermatocytes and spermatids. The protein plays a critical role in the assembly of the nexin-dynein regulatory complex. Mutations in this gene result in primary ciliary dyskinesia. [provided by RefSeq, Nov 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0584 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CCDC65 | ENST00000320516.5 | c.1370_1371delTT | p.Phe457fs | frameshift_variant | 8/8 | 1 | NM_033124.5 | ENSP00000312706.4 | ||
ENSG00000272822 | ENST00000398092.4 | c.385-17450_385-17449delAA | intron_variant | 3 | ENSP00000438507.1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152172Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251492Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135922
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GnomAD4 exome AF: 0.0000397 AC: 58AN: 1461888Hom.: 1 AF XY: 0.0000413 AC XY: 30AN XY: 727246
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152290Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74472
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia 27 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 13, 2016 | This sequence change deletes 2 nucleotides from exon 8 of the CCDC65 mRNA (c.1370_1371delTT), causing a frameshift at codon 457. This creates a premature translational stop signal in the last exon of the CCDC65 mRNA (p.Phe457Tyrfs*21). While this is not anticipated to result in nonsense mediated decay, it is expected to result in a truncated CCDC65 protein. 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. In summary, this variant is a novel truncation near the end of the CCDC65 protein that has uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. - |
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at