rs60978485
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_006846.4(SPINK5):c.603-49A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.039 in 1,515,472 control chromosomes in the GnomAD database, including 1,691 homozygotes. 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 0.034 ( 147 hom., cov: 32)
Exomes 𝑓: 0.040 ( 1544 hom. )
Consequence
SPINK5
NM_006846.4 intron
NM_006846.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.364
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 made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SPINK5 | NM_006846.4 | c.603-49A>T | intron_variant | ENST00000256084.8 | NP_006837.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SPINK5 | ENST00000256084.8 | c.603-49A>T | intron_variant | 1 | NM_006846.4 | ENSP00000256084.7 |
Frequencies
GnomAD3 genomes AF: 0.0338 AC: 5133AN: 151806Hom.: 147 Cov.: 32
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GnomAD3 exomes AF: 0.0450 AC: 10640AN: 236476Hom.: 364 AF XY: 0.0449 AC XY: 5762AN XY: 128398
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GnomAD4 exome AF: 0.0396 AC: 54040AN: 1363548Hom.: 1544 Cov.: 21 AF XY: 0.0402 AC XY: 27465AN XY: 683868
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GnomAD4 genome AF: 0.0338 AC: 5139AN: 151924Hom.: 147 Cov.: 32 AF XY: 0.0367 AC XY: 2722AN XY: 74260
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at