rs2303070
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_006846.4(SPINK5):c.2475G>A(p.Glu825Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,451,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SPINK5
NM_006846.4 synonymous
NM_006846.4 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.623
Publications
38 publications found
Genes affected
SPINK5 (HGNC:15464): (serine peptidase inhibitor Kazal type 5) This gene encodes a multidomain serine protease inhibitor that contains 15 potential inhibitory domains. The encoded preproprotein is proteolytically processed to generate multiple protein products, which may exhibit unique activities and specificities. These proteins may play a role in skin and hair morphogenesis, as well as anti-inflammatory and antimicrobial protection of mucous epithelia. Mutations in this gene may result in Netherton syndrome, a disorder characterized by ichthyosis, defective cornification, and atopy. This gene is present in a gene cluster on chromosome 5. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP7
Synonymous conserved (PhyloP=-0.623 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| SPINK5 | NM_006846.4 | c.2475G>A | p.Glu825Glu | synonymous_variant | Exon 26 of 33 | ENST00000256084.8 | NP_006837.2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| SPINK5 | ENST00000256084.8 | c.2475G>A | p.Glu825Glu | synonymous_variant | Exon 26 of 33 | 1 | NM_006846.4 | ENSP00000256084.7 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1451786Hom.: 0 Cov.: 35 AF XY: 0.00000277 AC XY: 2AN XY: 720906 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
2
AN:
1451786
Hom.:
Cov.:
35
AF XY:
AC XY:
2
AN XY:
720906
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33172
American (AMR)
AF:
AC:
0
AN:
43756
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25956
East Asian (EAS)
AF:
AC:
0
AN:
39288
South Asian (SAS)
AF:
AC:
1
AN:
84476
European-Finnish (FIN)
AF:
AC:
0
AN:
52856
Middle Eastern (MID)
AF:
AC:
0
AN:
5758
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1106504
Other (OTH)
AF:
AC:
1
AN:
60020
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
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>80
Age
GnomAD4 genome 0.00 AC: 0AN: 152032Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74314
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
152032
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
74314
African (AFR)
AF:
AC:
0
AN:
41488
American (AMR)
AF:
AC:
0
AN:
15278
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5138
South Asian (SAS)
AF:
AC:
0
AN:
4808
European-Finnish (FIN)
AF:
AC:
0
AN:
10560
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67974
Other (OTH)
AF:
AC:
0
AN:
2112
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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