chr12-48921079-C-A
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_033124.5(CCDC65):c.1176C>A(p.Thr392=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 1,609,902 control chromosomes in the GnomAD database, including 114,947 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.33 ( 9119 hom., cov: 31)
Exomes 𝑓: 0.37 ( 105828 hom. )
Consequence
CCDC65
NM_033124.5 synonymous
NM_033124.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0960
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 12-48921079-C-A is Benign according to our data. Variant chr12-48921079-C-A is described in ClinVar as [Benign]. Clinvar id is 402503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.096 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC65 | NM_033124.5 | c.1176C>A | p.Thr392= | synonymous_variant | 7/8 | ENST00000320516.5 | |
CCDC65 | NM_001286957.2 | c.747C>A | p.Thr249= | synonymous_variant | 7/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC65 | ENST00000320516.5 | c.1176C>A | p.Thr392= | synonymous_variant | 7/8 | 1 | NM_033124.5 | P2 | |
CCDC65 | ENST00000266984.9 | c.1176C>A | p.Thr392= | synonymous_variant | 7/9 | 5 | A2 | ||
CCDC65 | ENST00000552942.5 | c.867C>A | p.Thr289= | synonymous_variant | 5/6 | 5 | |||
CCDC65 | ENST00000547861.5 | c.*1007C>A | 3_prime_UTR_variant, NMD_transcript_variant | 7/8 | 2 |
Frequencies
GnomAD3 genomes AF: 0.326 AC: 49549AN: 151890Hom.: 9111 Cov.: 31
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GnomAD3 exomes AF: 0.382 AC: 95332AN: 249870Hom.: 19790 AF XY: 0.373 AC XY: 50460AN XY: 135228
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GnomAD4 exome AF: 0.375 AC: 546543AN: 1457894Hom.: 105828 Cov.: 44 AF XY: 0.371 AC XY: 269081AN XY: 724668
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GnomAD4 genome AF: 0.326 AC: 49568AN: 152008Hom.: 9119 Cov.: 31 AF XY: 0.330 AC XY: 24508AN XY: 74296
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia 27 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 10, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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