rs17774892

Variant names:

• chr5-148035405-A-G
• rs17774892
• ENST00000521206.5:c.-183+9619A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000521206.5(SPINK5):​c.-183+9619A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0385 in 152,298 control chromosomes in the GnomAD database, including 188 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 0.038 (188 hom., cov: 32)
• Consequence: SPINK5 ENST00000521206.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550
• Publications: 1 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]

SPINK5 Gene-Disease associations (from GenCC):

• Netherton syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPINK5	ENST00000521206.5	c.-183+9619A>G		intron_variant	Intron 1 of 4	4		ENSP00000430264.1

Frequencies

GnomAD3 genomes AF: 0.0385 AC: 5858 AN: 152180 Hom.: 188 Cov.: 32

Gnomad AFR AF: 0.00806

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0593

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.0617

Gnomad FIN AF: 0.0629

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0406

Gnomad OTH AF: 0.0263

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

GnomAD4 genome AF: 0.0385 AC: 5863 AN: 152298 Hom.: 188 Cov.: 32 AF XY: 0.0412 AC XY: 3070 AN XY: 74464

African (AFR) AF: 0.00803 AC: 334 AN: 41582

American (AMR) AF: 0.0595 AC: 910 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0412 AC: 143 AN: 3470

East Asian (EAS) AF: 0.130 AC: 673 AN: 5176

South Asian (SAS) AF: 0.0623 AC: 301 AN: 4828

European-Finnish (FIN) AF: 0.0629 AC: 667 AN: 10604

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0406 AC: 2764 AN: 68032

Other (OTH) AF: 0.0260 AC: 55 AN: 2112

Alfa AF: 0.0412 Hom.: 61

Bravo AF: 0.0354

Asia WGS AF: 0.0820 AC: 286 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.7
DANN	Benign	0.86
PhyloP100		-0.055

Splicing

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

Other links and lift over

dbSNP: rs17774892; hg19: chr5-147414968;