rs17107650

Variant names:

• chr5-148036835-G-T
• rs17107650
• ENST00000521206.5:c.-183+11049G>T

Variant summary

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

The ENST00000521206.5(SPINK5):​c.-183+11049G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 151,390 control chromosomes in the GnomAD database, including 1,721 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 0.11 (1721 hom., cov: 31)
• Consequence: SPINK5 ENST00000521206.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.264 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+11049G>T		intron_variant	Intron 1 of 4	4		ENSP00000430264.1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17171 AN: 151282 Hom.: 1711 Cov.: 31

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0888

Gnomad ASJ AF: 0.0502

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.0623

Gnomad FIN AF: 0.0629

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0417

Gnomad OTH AF: 0.0815

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

GnomAD4 genome AF: 0.114 AC: 17231 AN: 151390 Hom.: 1721 Cov.: 31 AF XY: 0.114 AC XY: 8405 AN XY: 73962

African (AFR) AF: 0.269 AC: 11065 AN: 41210

American (AMR) AF: 0.0890 AC: 1351 AN: 15172

Ashkenazi Jewish (ASJ) AF: 0.0502 AC: 174 AN: 3464

East Asian (EAS) AF: 0.129 AC: 663 AN: 5134

South Asian (SAS) AF: 0.0629 AC: 302 AN: 4798

European-Finnish (FIN) AF: 0.0629 AC: 657 AN: 10444

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0417 AC: 2830 AN: 67868

Other (OTH) AF: 0.0806 AC: 169 AN: 2096

Alfa AF: 0.0628 Hom.: 291

Bravo AF: 0.122

Asia WGS AF: 0.0990 AC: 346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.15
DANN	Benign	0.31
PhyloP100		-0.21

Splicing

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

Other links and lift over

dbSNP: rs17107650; hg19: chr5-147416398;