5-148064089-C-A
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_006846.4(SPINK5):c.45C>A(p.Cys15*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,848 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 Pathogenic (★).
Frequency
Consequence
NM_006846.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SPINK5 | NM_006846.4 | c.45C>A | p.Cys15* | stop_gained | Exon 1 of 33 | ENST00000256084.8 | NP_006837.2 | |
SPINK5 | NM_001127698.2 | c.45C>A | p.Cys15* | stop_gained | Exon 1 of 34 | NP_001121170.1 | ||
SPINK5 | NM_001127699.2 | c.45C>A | p.Cys15* | stop_gained | Exon 1 of 28 | NP_001121171.1 | ||
SPINK5 | XM_047416662.1 | c.45C>A | p.Cys15* | stop_gained | Exon 1 of 34 | XP_047272618.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249496Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135358
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461848Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 727226
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Ichthyosis linearis circumflexa Pathogenic:1
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with SPINK5-related conditions. This variant is present in population databases (rs770450773, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Cys15*) in the SPINK5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SPINK5 are known to be pathogenic (PMID: 11511292, 11841556). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at