5-148033937-T-G

Variant summary

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

The ENST00000521206.5(SPINK5):c.-183+8151T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,170 control chromosomes in the GnomAD database, including 2,806 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 0.14 (2806 hom., cov: 32)
• Consequence: SPINK5 ENST00000521206.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPINK5	ENST00000521206.5	c.-183+8151T>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20689 AN: 152052 Hom.: 2785 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0954

Gnomad ASJ AF: 0.0501

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.0620

Gnomad FIN AF: 0.0634

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0421

Gnomad OTH AF: 0.0932

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

GnomAD4 genome AF: 0.136 AC: 20768 AN: 152170 Hom.: 2806 Cov.: 32 AF XY: 0.136 AC XY: 10090 AN XY: 74396

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.0956

Gnomad4 ASJ AF: 0.0501

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.0626

Gnomad4 FIN AF: 0.0634

Gnomad4 NFE AF: 0.0421

Gnomad4 OTH AF: 0.0922

Alfa AF: 0.0530 Hom.: 884

Bravo AF: 0.148

Asia WGS AF: 0.106 AC: 370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	4.0
Dann	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11948836; hg19: chr5-147413500;