NM_001264.5:c.164_167dupGCCT
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_Strong
The NM_001264.5(CDSN):c.164_167dupGCCT(p.Thr57ProfsTer6) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000963 in 1,557,874 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001264.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDSN | NM_001264.5 | c.164_167dupGCCT | p.Thr57ProfsTer6 | frameshift_variant | Exon 2 of 2 | ENST00000376288.3 | NP_001255.4 | |
PSORS1C1 | NM_014068.3 | c.-229+2560_-229+2563dupCAGG | intron_variant | Intron 1 of 5 | ENST00000259881.10 | NP_054787.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CDSN | ENST00000376288.3 | c.164_167dupGCCT | p.Thr57ProfsTer6 | frameshift_variant | Exon 2 of 2 | 1 | NM_001264.5 | ENSP00000365465.2 | ||
PSORS1C1 | ENST00000259881.10 | c.-229+2560_-229+2563dupCAGG | intron_variant | Intron 1 of 5 | 1 | NM_014068.3 | ENSP00000259881.9 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152218Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000309 AC: 5AN: 161622Hom.: 0 AF XY: 0.0000232 AC XY: 2AN XY: 86158
GnomAD4 exome AF: 0.00000996 AC: 14AN: 1405656Hom.: 0 Cov.: 54 AF XY: 0.0000101 AC XY: 7AN XY: 694034
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152218Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74370
ClinVar
Submissions by phenotype
Peeling skin syndrome 1 Pathogenic:1
- -
not provided Uncertain:1
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 157564). This premature translational stop signal has been observed in individuals with autosomal recessive peeling skin syndrome (PMID: 22146835, 31663161). This variant is present in population databases (rs606231274, gnomAD 0.06%). This sequence change creates a premature translational stop signal (p.Thr57Profs*6) in the CDSN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 473 amino acid(s) of the CDSN protein. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at