rs12332673

Variant names:

• chr5-148027816-G-A
• rs12332673
• ENST00000521206.5:c.-183+2030G>A

Variant summary

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

The ENST00000521206.5(SPINK5):​c.-183+2030G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 151,974 control chromosomes in the GnomAD database, including 5,724 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 0.18 (5724 hom., cov: 32)
• Consequence: SPINK5 ENST00000521206.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 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+2030G>A		intron_variant	Intron 1 of 4	4		ENSP00000430264.1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27740 AN: 151856 Hom.: 5697 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0501

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.0627

Gnomad FIN AF: 0.0635

Gnomad MID AF: 0.0350

Gnomad NFE AF: 0.0423

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.183 AC: 27828 AN: 151974 Hom.: 5724 Cov.: 32 AF XY: 0.181 AC XY: 13429 AN XY: 74286

African (AFR) AF: 0.510 AC: 21126 AN: 41430

American (AMR) AF: 0.112 AC: 1718 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0501 AC: 174 AN: 3472

East Asian (EAS) AF: 0.131 AC: 675 AN: 5170

South Asian (SAS) AF: 0.0633 AC: 305 AN: 4816

European-Finnish (FIN) AF: 0.0635 AC: 671 AN: 10562

Middle Eastern (MID) AF: 0.0342 AC: 10 AN: 292

European-Non Finnish (NFE) AF: 0.0423 AC: 2877 AN: 67938

Other (OTH) AF: 0.123 AC: 259 AN: 2108

Alfa AF: 0.0841 Hom.: 803

Bravo AF: 0.202

Asia WGS AF: 0.114 AC: 398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.2
DANN	Benign	0.56
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs12332673; hg19: chr5-147407379;