rs727504989
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_001146079.2(CLDN14):c.83C>T(p.Pro28Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,601,958 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 Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P28P) has been classified as Likely benign.
Frequency
Consequence
NM_001146079.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLDN14 | NM_001146079.2 | c.83C>T | p.Pro28Leu | missense_variant | 2/2 | ENST00000399135.6 | |
CLDN14-AS1 | NR_183529.1 | n.468+15606G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLDN14 | ENST00000399135.6 | c.83C>T | p.Pro28Leu | missense_variant | 2/2 | 1 | NM_001146079.2 | P1 | |
CLDN14-AS1 | ENST00000428667.1 | n.277+15606G>A | intron_variant, non_coding_transcript_variant | 5 | |||||
LNCTSI | ENST00000429588.1 | n.54-18618G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152166Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000178 AC: 4AN: 224682Hom.: 0 AF XY: 0.0000245 AC XY: 3AN XY: 122252
GnomAD4 exome AF: 0.0000131 AC: 19AN: 1449674Hom.: 0 Cov.: 33 AF XY: 0.0000125 AC XY: 9AN XY: 720278
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152284Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74472
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 15, 2014 | The Pro28Leu variant in CLDN14 has not been previously reported in individuals w ith hearing loss or in large population studies. Computational prediction tools and conservation analyses suggest that the Pro28Leu variant may impact the prot ein, though this information is not predictive enough to determine pathogenicity . In summary, additional information is needed to fully assess the clinical sign ificance of this variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at