rs10463396

Variant names:

• chr5-148035779-A-G
• rs10463396
• ENST00000521206.5:c.-183+9993A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-148035779-A-G
• chr5-148035779-A-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+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
• Publications: 2 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000521206.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPINK5	ENST00000521206.5	TSL:4	c.-183+9993A>G		intron	N/A	ENSP00000430264.1

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

African (AFR) AF: 0.327 AC: 13547 AN: 41452

American (AMR) AF: 0.626 AC: 9556 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1980 AN: 3468

East Asian (EAS) AF: 0.778 AC: 4018 AN: 5164

South Asian (SAS) AF: 0.783 AC: 3771 AN: 4816

European-Finnish (FIN) AF: 0.598 AC: 6326 AN: 10572

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 38016 AN: 67926

Other (OTH) AF: 0.576 AC: 1215 AN: 2108

Alfa AF: 0.545 Hom.: 11683

Bravo AF: 0.516

Asia WGS AF: 0.757 AC: 2627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.1
DANN	Benign	0.84
PhyloP100		0.33

Splicing

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

Other links and lift over

dbSNP: rs10463396; hg19: chr5-147415342;