5-148064046-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PVS1_SupportingPM2
The NM_006846.4(SPINK5):c.2T>A(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_006846.4 start_lost
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SPINK5 | NM_006846.4 | c.2T>A | p.Met1? | start_lost | Exon 1 of 33 | ENST00000256084.8 | NP_006837.2 | |
SPINK5 | NM_001127698.2 | c.2T>A | p.Met1? | start_lost | Exon 1 of 34 | NP_001121170.1 | ||
SPINK5 | NM_001127699.2 | c.2T>A | p.Met1? | start_lost | Exon 1 of 28 | NP_001121171.1 | ||
SPINK5 | XM_047416662.1 | c.2T>A | p.Met1? | start_lost | Exon 1 of 34 | XP_047272618.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Ichthyosis linearis circumflexa Uncertain:1
This variant has not been reported in the literature in individuals affected with SPINK5-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts a region of the SPINK5 protein in which other variant(s) (p.Gln27Arg) have been observed in individuals with SPINK5-related conditions (PMID: 33452875; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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. This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the SPINK5 mRNA. The next in-frame methionine is located at codon 29. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.