rs17718511

Positions:

• chr5-148072009-A-G

Variant summary

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

The NM_006846.4(SPINK5):​c.210-139A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0428 in 733,196 control chromosomes in the GnomAD database, including 1,108 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 0.034 (148 hom., cov: 32)
  • Exomes 𝑓: 0.045 (960 hom.)
• Consequence: SPINK5 NM_006846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.424

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPINK5	NM_006846.4	c.210-139A>G		intron_variant		ENST00000256084.8	NP_006837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPINK5	ENST00000256084.8	c.210-139A>G		intron_variant		1	NM_006846.4	ENSP00000256084.7

Frequencies

GnomAD3 genomes AF: 0.0338 AC: 5134 AN: 152004 Hom.: 148 Cov.: 32

Gnomad AFR AF: 0.00702

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0536

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.0668

Gnomad FIN AF: 0.0573

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0335

Gnomad OTH AF: 0.0234

GnomAD4 exome AF: 0.0452 AC: 26245 AN: 581074 Hom.: 960 AF XY: 0.0455 AC XY: 14180 AN XY: 311930

Gnomad4 AFR exome AF: 0.00626

Gnomad4 AMR exome AF: 0.0534

Gnomad4 ASJ exome AF: 0.0299

Gnomad4 EAS exome AF: 0.165

Gnomad4 SAS exome AF: 0.0615

Gnomad4 FIN exome AF: 0.0527

Gnomad4 NFE exome AF: 0.0335

Gnomad4 OTH exome AF: 0.0346

GnomAD4 genome AF: 0.0338 AC: 5140 AN: 152122 Hom.: 148 Cov.: 32 AF XY: 0.0366 AC XY: 2725 AN XY: 74362

Gnomad4 AFR AF: 0.00700

Gnomad4 AMR AF: 0.0538

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.0677

Gnomad4 FIN AF: 0.0573

Gnomad4 NFE AF: 0.0335

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.0324 Hom.: 17

Bravo AF: 0.0311

Asia WGS AF: 0.0850 AC: 296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs17718511; hg19: chr5-147451572;