rs777112652
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_003672.4(CDC14A):c.1015C>T(p.Arg339Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000119 in 1,596,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_003672.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDC14A | NM_003672.4 | c.1015C>T | p.Arg339Ter | stop_gained | 11/16 | ENST00000336454.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDC14A | ENST00000336454.5 | c.1015C>T | p.Arg339Ter | stop_gained | 11/16 | 1 | NM_003672.4 | A1 | |
ENST00000432210.1 | n.82+1587G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151952Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000847 AC: 2AN: 236146Hom.: 0 AF XY: 0.00000781 AC XY: 1AN XY: 128002
GnomAD4 exome AF: 0.0000125 AC: 18AN: 1444974Hom.: 0 Cov.: 30 AF XY: 0.00000835 AC XY: 6AN XY: 718706
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151952Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74214
ClinVar
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 32 Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 03, 2018 | - - |
Pathogenic, criteria provided, single submitter | curation | SIB Swiss Institute of Bioinformatics | Nov 05, 2018 | This variant is interpreted as a Pathogenic for Deafness, autosomal recessive 32, with or without immotile sperm. The following ACMG Tag(s) were applied: PM2 : Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PVS1-Strong : PVS1 downgraded in strength to Strong. PP1-Strong : Segregation data PP1 upgraded to strong (PMID:27259055). - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Feb 09, 2022 | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 27259055, 31906439) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at