rs1187237772
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_033124.5(CCDC65):c.144_164del(p.Lys49_Ala55del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A48A) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Consequence
CCDC65
NM_033124.5 inframe_deletion
NM_033124.5 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.41
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_033124.5.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC65 | NM_033124.5 | c.144_164del | p.Lys49_Ala55del | inframe_deletion | 2/8 | ENST00000320516.5 | |
CCDC65 | NM_001286957.2 | c.-279-7_-266del | splice_acceptor_variant, 5_prime_UTR_variant, intron_variant | 2/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC65 | ENST00000320516.5 | c.144_164del | p.Lys49_Ala55del | inframe_deletion | 2/8 | 1 | NM_033124.5 | P2 | |
CCDC65 | ENST00000266984.9 | c.144_164del | p.Lys49_Ala55del | inframe_deletion | 2/9 | 5 | A2 | ||
CCDC65 | ENST00000552942.5 | c.144_164del | p.Lys49_Ala55del | inframe_deletion | 2/6 | 5 | |||
CCDC65 | ENST00000547861.5 | c.111-7_124del | splice_acceptor_variant, coding_sequence_variant, intron_variant, NMD_transcript_variant | 2/8 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Bravo
AF:
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 | Invitae | Oct 18, 2017 | 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. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acids is currently unknown. This variant has not been reported in the literature in individuals with CCDC65-related disease. This variant is not present in population databases (ExAC no frequency). This variant, c.144_164del, results in the deletion of 7 amino acids of the CCDC65 protein (p.Lys49_Ala55del), but otherwise preserves the integrity of the reading frame. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at