chr10-71712674-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM1BP4_Moderate
The NM_022124.6(CDH23):c.3230C>T(p.Pro1077Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000824 in 1,613,634 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1077R) has been classified as Uncertain significance.
Frequency
Consequence
NM_022124.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH23 | NM_022124.6 | c.3230C>T | p.Pro1077Leu | missense_variant | 28/70 | ENST00000224721.12 | |
C10orf105 | NM_001164375.3 | c.*3262G>A | 3_prime_UTR_variant | 2/2 | ENST00000441508.4 | ||
CDH23 | NM_001171930.2 | c.3230C>T | p.Pro1077Leu | missense_variant | 28/32 | ||
C10orf105 | NM_001168390.2 | c.*3262G>A | 3_prime_UTR_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH23 | ENST00000224721.12 | c.3230C>T | p.Pro1077Leu | missense_variant | 28/70 | 5 | NM_022124.6 | P1 | |
C10orf105 | ENST00000441508.4 | c.*3262G>A | 3_prime_UTR_variant | 2/2 | 1 | NM_001164375.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000381 AC: 58AN: 152242Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000125 AC: 31AN: 248514Hom.: 0 AF XY: 0.0000592 AC XY: 8AN XY: 135036
GnomAD4 exome AF: 0.0000513 AC: 75AN: 1461274Hom.: 0 Cov.: 31 AF XY: 0.0000440 AC XY: 32AN XY: 726922
GnomAD4 genome AF: 0.000381 AC: 58AN: 152360Hom.: 0 Cov.: 33 AF XY: 0.000389 AC XY: 29AN XY: 74508
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 28, 2021 | In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 25, 2015 | The p.Pro1077Leu variant in CDH23 has been identified by our laboratory in one i ndividual with sensorineural hearing loss, who did not carry a second CDH23 vari ant (LMM unpublished data). The variant has been identified in 0.16% (15/9416) o f African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.bro adinstitute.org; dbSNP rs202101019); however, this frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation a nalysis suggest that this variant may impact the protein, though this informatio n is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Pro1077Leu variant is uncertain. - |
Usher syndrome type 1 Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Mar 03, 2020 | - - |
Retinal dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Blueprint Genetics | Oct 22, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at