rs144666367
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PVS1_StrongBS2
The NM_002640.4(SERPINB8):c.850C>T(p.Arg284*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000452 in 1,614,170 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_002640.4 stop_gained
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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SERPINB8 | NM_002640.4 | c.850C>T | p.Arg284* | stop_gained | Exon 7 of 7 | ENST00000397985.7 | NP_002631.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000381 AC: 58AN: 152164Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000612 AC: 154AN: 251494Hom.: 0 AF XY: 0.000633 AC XY: 86AN XY: 135920
GnomAD4 exome AF: 0.000459 AC: 671AN: 1461888Hom.: 2 Cov.: 30 AF XY: 0.000457 AC XY: 332AN XY: 727246
GnomAD4 genome AF: 0.000381 AC: 58AN: 152282Hom.: 0 Cov.: 32 AF XY: 0.000376 AC XY: 28AN XY: 74468
ClinVar
Submissions by phenotype
Peeling skin syndrome 5 Pathogenic:2Uncertain:1
NM_002640.3:c.850C>T in the SERPINB8 gene has an allele frequency of 0.012 in Ashkenazi Jewish subpopulation in the gnomAD database. This variant is located in the last exon and may not lead to nonsense-mediated mRNA decay. It was detected in individual with autosomal recessive Peeling skin syndrome 5 in a pedigree, three homozygous c.850C>T, five carriers. And their parents are carriers (PMID: 27476651). The patient's phenotype is highly specific for SERPINB8 gene(PMID: 27476651). Taken together, we interprete this variant as Pathogenic/Likely pathogenic. ACMG/AMP criteria applied: PM3_Supporting; PP4; PP1_Strong. -
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not provided Uncertain:1
This sequence change creates a premature translational stop signal (p.Arg284*) in the SERPINB8 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 91 amino acid(s) of the SERPINB8 protein. This variant is present in population databases (rs144666367, gnomAD 1.2%), and has an allele count higher than expected for a pathogenic variant. This premature translational stop signal has been observed in individual(s) with exfoliative ichthyosis (PMID: 27476651). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 254200). 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at