rs138153104
Variant summary
Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_178335.3(CCDC50):c.617C>T(p.Ser206Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00121 in 1,613,812 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_178335.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Our verdict: Benign. The variant received -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CCDC50 | NM_178335.3 | c.617C>T | p.Ser206Phe | missense_variant | Exon 6 of 12 | ENST00000392455.9 | NP_848018.1 | |
CCDC50 | XM_011512460.2 | c.617C>T | p.Ser206Phe | missense_variant | Exon 6 of 8 | XP_011510762.1 | ||
CCDC50 | NM_174908.4 | c.449-4929C>T | intron_variant | Intron 5 of 10 | NP_777568.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000815 AC: 124AN: 152138Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.000699 AC: 175AN: 250516 AF XY: 0.000731 show subpopulations
GnomAD4 exome AF: 0.00125 AC: 1834AN: 1461556Hom.: 3 Cov.: 31 AF XY: 0.00125 AC XY: 908AN XY: 727070 show subpopulations
GnomAD4 genome AF: 0.000814 AC: 124AN: 152256Hom.: 0 Cov.: 32 AF XY: 0.000725 AC XY: 54AN XY: 74444 show subpopulations
ClinVar
Submissions by phenotype
not specified Uncertain:2Benign:1
The c.617C>T (p.S206F) alteration is located in exon 6 (coding exon 6) of the CCDC50 gene. This alteration results from a C to T substitution at nucleotide position 617, causing the serine (S) at amino acid position 206 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Variant classified as Uncertain Significance - Favor Benign. The p.Ser206Phe var iant in CCDC50 has been previously identified by our laboratory in two individua ls with hearing loss, one of whom had an alternate genetic etiology for their he aring loss (LMM data). This variant has also been identified in 0.12% (154/12597 2) of European chromosomes by the Genome Aggregation Database (gnomAD, http://gn omad.broadinstitute.org; dbSNP rs138153104). Although this variant has been seen in the general population, its frequency is not high enough to rule out a patho genic role. Computational prediction tools and conservation analysis suggest tha t the p.Ser206Phe variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, while the clinical significance of the p.Ser206Phe variant is uncertain, these data suggest that i t is more likely to be benign. ACMG/AMP Criteria applied: BP4. -
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not provided Benign:3
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CCDC50: BP4, BS1, BS2 -
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CCDC50-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at