rs118060953
Positions:
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_033124.5(CCDC65):āc.203T>Cā(p.Val68Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00143 in 1,614,042 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0012 ( 0 hom., cov: 32)
Exomes š: 0.0015 ( 2 hom. )
Consequence
CCDC65
NM_033124.5 missense
NM_033124.5 missense
Scores
7
10
Clinical Significance
Conservation
PhyloP100: 4.38
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 Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.01739201).
BP6
?
Variant 12-48905016-T-C is Benign according to our data. Variant chr12-48905016-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 474636.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC65 | NM_033124.5 | c.203T>C | p.Val68Ala | missense_variant | 2/8 | ENST00000320516.5 | |
CCDC65 | NM_001286957.2 | c.-227T>C | 5_prime_UTR_variant | 2/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC65 | ENST00000320516.5 | c.203T>C | p.Val68Ala | missense_variant | 2/8 | 1 | NM_033124.5 | P2 | |
CCDC65 | ENST00000266984.9 | c.203T>C | p.Val68Ala | missense_variant | 2/9 | 5 | A2 | ||
CCDC65 | ENST00000552942.5 | c.203T>C | p.Val68Ala | missense_variant | 2/6 | 5 | |||
CCDC65 | ENST00000547861.5 | c.*34T>C | 3_prime_UTR_variant, NMD_transcript_variant | 2/8 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00122 AC: 185AN: 152156Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.00125 AC: 314AN: 251394Hom.: 3 AF XY: 0.00110 AC XY: 149AN XY: 135868
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GnomAD4 exome AF: 0.00145 AC: 2125AN: 1461768Hom.: 2 Cov.: 31 AF XY: 0.00137 AC XY: 996AN XY: 727170
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GnomAD4 genome ? AF: 0.00121 AC: 185AN: 152274Hom.: 0 Cov.: 32 AF XY: 0.00125 AC XY: 93AN XY: 74454
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia 27 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Mar 09, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | CCDC65: BP4 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
T;D;T
Polyphen
0.87
.;.;P
Vest4
MVP
MPC
0.069
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at