rs876657435
Positions:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_178335.3(CCDC50):c.804G>A(p.Gln268Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Consequence
CCDC50
NM_178335.3 synonymous
NM_178335.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.880
Genes affected
CCDC50 (HGNC:18111): (coiled-coil domain containing 50) This gene encodes a soluble, cytoplasmic, tyrosine-phosphorylated protein with multiple ubiquitin-interacting domains. Mutations in this gene cause nonsyndromic, postlingual, progressive sensorineural DFNA44 hearing loss. In mouse, the protein is expressed in the inner ear during development and postnatal maturation and associates with microtubule-based structures. This protein may also function as a negative regulator of NF-kB signaling and as an effector of epidermal growth factor (EGF)-mediated cell signaling. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
Variant 3-191375417-G-A is Benign according to our data. Variant chr3-191375417-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 227213.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.88 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CCDC50 | NM_178335.3 | c.804G>A | p.Gln268Gln | synonymous_variant | 6/12 | ENST00000392455.9 | NP_848018.1 | |
CCDC50 | XM_011512460.2 | c.804G>A | p.Gln268Gln | synonymous_variant | 6/8 | XP_011510762.1 | ||
CCDC50 | NM_174908.4 | c.449-4742G>A | intron_variant | NP_777568.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CCDC50 | ENST00000392455.9 | c.804G>A | p.Gln268Gln | synonymous_variant | 6/12 | 1 | NM_178335.3 | ENSP00000376249.4 | ||
CCDC50 | ENST00000392456.4 | c.449-4742G>A | intron_variant | 1 | ENSP00000376250.4 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152110Hom.: 0 Cov.: 31
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GnomAD4 exome Cov.: 62
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152110Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74298
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 24, 2015 | p.Gln268Gln variant in exon 6 of CCDC50: This variant is not expected to have cl inical significance because it does not alter an amino acid residue and is not l ocated within the splice consensus sequence. - |
Computational scores
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Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at