rs121908542
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PM5PP3
The NM_006580.4(CLDN16):c.698C>A(p.Thr233Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,844 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T233R) has been classified as Pathogenic.
Frequency
Consequence
NM_006580.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLDN16 | NM_006580.4 | c.698C>A | p.Thr233Lys | missense_variant | 5/5 | ENST00000264734.3 | |
CLDN16 | NM_001378492.1 | c.698C>A | p.Thr233Lys | missense_variant | 9/9 | ||
CLDN16 | NM_001378493.1 | c.698C>A | p.Thr233Lys | missense_variant | 8/8 | ||
CLDN16 | XM_047447333.1 | c.698C>A | p.Thr233Lys | missense_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLDN16 | ENST00000264734.3 | c.698C>A | p.Thr233Lys | missense_variant | 5/5 | 1 | NM_006580.4 | P1 | |
CLDN16 | ENST00000456423.2 | downstream_gene_variant | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461844Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727216
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 15, 2022 | The c.908C>A (p.T303K) alteration is located in exon 5 (coding exon 5) of the CLDN16 gene. This alteration results from a C to A substitution at nucleotide position 908, causing the threonine (T) at amino acid position 303 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at