7-73831422-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001305.5(CLDN4):c.221C>T(p.Pro74Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000508 in 1,614,024 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001305.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CLDN4 | ENST00000340958.4 | c.221C>T | p.Pro74Leu | missense_variant | Exon 1 of 1 | 6 | NM_001305.5 | ENSP00000342445.2 | ||
CLDN4 | ENST00000431918.1 | c.221C>T | p.Pro74Leu | missense_variant | Exon 2 of 2 | 2 | ENSP00000388639.1 | |||
CLDN4 | ENST00000435050.1 | c.221C>T | p.Pro74Leu | missense_variant | Exon 2 of 2 | 2 | ENSP00000409544.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152240Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251252Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135832
GnomAD4 exome AF: 0.0000547 AC: 80AN: 1461784Hom.: 0 Cov.: 33 AF XY: 0.0000605 AC XY: 44AN XY: 727202
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152240Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74384
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.221C>T (p.P74L) alteration is located in exon 1 (coding exon 1) of the CLDN4 gene. This alteration results from a C to T substitution at nucleotide position 221, causing the proline (P) at amino acid position 74 to be replaced by a leucine (L). 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