5-148065350-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006846.4(SPINK5):c.59C>T(p.Ala20Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_006846.4 missense
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/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SPINK5 | NM_006846.4 | c.59C>T | p.Ala20Val | missense_variant | 2/33 | ENST00000256084.8 | NP_006837.2 | |
SPINK5 | NM_001127698.2 | c.59C>T | p.Ala20Val | missense_variant | 2/34 | NP_001121170.1 | ||
SPINK5 | NM_001127699.2 | c.59C>T | p.Ala20Val | missense_variant | 2/28 | NP_001121171.1 | ||
SPINK5 | XM_047416662.1 | c.59C>T | p.Ala20Val | missense_variant | 2/34 | XP_047272618.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SPINK5 | ENST00000256084.8 | c.59C>T | p.Ala20Val | missense_variant | 2/33 | 1 | NM_006846.4 | ENSP00000256084 | P2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000482 AC: 12AN: 248878Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135046
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461062Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 726824
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Netherton syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 09, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 20 of the SPINK5 protein (p.Ala20Val). This variant is present in population databases (rs777592836, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with SPINK5-related conditions. ClinVar contains an entry for this variant (Variation ID: 660065). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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