rs375641853
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBP6
The NM_022124.6(CDH23):c.4498T>A(p.Ser1500Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,613,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. S1500S) has been classified as Likely benign.
Frequency
Consequence
NM_022124.6 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH23 | NM_022124.6 | c.4498T>A | p.Ser1500Thr | missense_variant | 37/70 | ENST00000224721.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH23 | ENST00000224721.12 | c.4498T>A | p.Ser1500Thr | missense_variant | 37/70 | 5 | NM_022124.6 | P1 | |
CDH23 | ENST00000398792.3 | n.1187T>A | non_coding_transcript_exon_variant | 8/9 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000145 AC: 22AN: 152212Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000482 AC: 12AN: 248940Hom.: 0 AF XY: 0.0000518 AC XY: 7AN XY: 135142
GnomAD4 exome AF: 0.0000212 AC: 31AN: 1461464Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727032
GnomAD4 genome ? AF: 0.000144 AC: 22AN: 152330Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10AN XY: 74500
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 | Jun 21, 2011 | Variant classified as Uncertain Significance - Favor Benign. The Ser1500Thr vari ant in CDH23 has not been reported in the literature nor previously identified b y our laboratory. This residue is not highly conserved in mammals and computatio nal analyses (PolyPhen2, SIFT, AlignGVGD) do not suggest a high likelihood of im pact to the protein. However, this information is not predictive enough to rule out pathogenicity. It should be noted that this lab has only sequenced CDH23 in 15 Black probands and no Black healthy controls. In addition, healthy control in formation is limited in either public databases or scientific literature, such t hat the full spectrum of benign variation has not yet been defined for this gene . Future analysis could reveal that the Leu2009His variant is common in this pop ulation and therefore unlikely to be pathogenic. In summary, the clinical signif icance of this variant cannot be determined with certainty at this time. - |
Usher syndrome type 1 Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at