5-148041925-A-C

Position:

• chr5-148041925-A-C

Variant summary

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

The ENST00000521206.5(SPINK5):​c.-183+16139A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0956 in 152,178 control chromosomes in the GnomAD database, including 1,069 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 0.096 (1069 hom., cov: 32)
• Consequence: SPINK5 ENST00000521206.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.531

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.201 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+16139A>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0953 AC: 14491 AN: 152058 Hom.: 1063 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0836

Gnomad ASJ AF: 0.0482

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.0619

Gnomad FIN AF: 0.0633

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0414

Gnomad OTH AF: 0.0699

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

GnomAD4 genome AF: 0.0956 AC: 14542 AN: 152178 Hom.: 1069 Cov.: 32 AF XY: 0.0960 AC XY: 7141 AN XY: 74416

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.0838

Gnomad4 ASJ AF: 0.0482

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.0625

Gnomad4 FIN AF: 0.0633

Gnomad4 NFE AF: 0.0414

Gnomad4 OTH AF: 0.0691

Alfa AF: 0.0477 Hom.: 491

Bravo AF: 0.101

Asia WGS AF: 0.0970 AC: 338 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	5.5
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17107673; hg19: chr5-147421488;