rs10463396

chr5-148035779-A-Gchr5-148035779-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000521206.5(SPINK5):c.-183+9993A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 151,976 control chromosomes in the GnomAD database, including 21,950 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 0.52 (21950 hom., cov: 32)
• Consequence: SPINK5 ENST00000521206.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.327

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPINK5	ENST00000521206.5	c.-183+9993A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79150 AN: 151858 Hom.: 21956 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.785

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.572

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.521 AC: 79157 AN: 151976 Hom.: 21950 Cov.: 32 AF XY: 0.530 AC XY: 39398 AN XY: 74266

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.626

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.778

Gnomad4 SAS AF: 0.783

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.560

Gnomad4 OTH AF: 0.576

Alfa AF: 0.547 Hom.: 10451

Bravo AF: 0.516

Asia WGS AF: 0.757 AC: 2627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	1.1
Dann	Benign	0.84

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10463396; hg19: chr5-147415342;