chr5-148063880-G-A

Position:

• chr5-148063880-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000521206.5(SPINK5):​c.-165G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0258 in 714,872 control chromosomes in the GnomAD database, including 491 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (46 hom., cov: 32)
  • Exomes 𝑓: 0.028 (445 hom.)
• Consequence: SPINK5 ENST00000521206.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.25

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 5-148063880-G-A is Benign according to our data. Variant chr5-148063880-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1218110.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.148063880G>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPINK5	ENST00000521206.5	c.-165G>A		5_prime_UTR_variant	2/5	4		ENSP00000430264.1

Frequencies

GnomAD3 genomes AF: 0.0176 AC: 2672 AN: 152152 Hom.: 44 Cov.: 32

Gnomad AFR AF: 0.00734

Gnomad AMI AF: 0.00989

Gnomad AMR AF: 0.0128

Gnomad ASJ AF: 0.0254

Gnomad EAS AF: 0.0442

Gnomad SAS AF: 0.0995

Gnomad FIN AF: 0.0126

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0172

Gnomad OTH AF: 0.0239

GnomAD4 exome AF: 0.0280 AC: 15746 AN: 562602 Hom.: 445 Cov.: 6 AF XY: 0.0326 AC XY: 9821 AN XY: 301608

Gnomad4 AFR exome AF: 0.00994

Gnomad4 AMR exome AF: 0.0129

Gnomad4 ASJ exome AF: 0.0286

Gnomad4 EAS exome AF: 0.0331

Gnomad4 SAS exome AF: 0.0981

Gnomad4 FIN exome AF: 0.0120

Gnomad4 NFE exome AF: 0.0184

Gnomad4 OTH exome AF: 0.0244

GnomAD4 genome AF: 0.0175 AC: 2669 AN: 152270 Hom.: 46 Cov.: 32 AF XY: 0.0182 AC XY: 1352 AN XY: 74452

Gnomad4 AFR AF: 0.00739

Gnomad4 AMR AF: 0.0128

Gnomad4 ASJ AF: 0.0254

Gnomad4 EAS AF: 0.0439

Gnomad4 SAS AF: 0.0990

Gnomad4 FIN AF: 0.0126

Gnomad4 NFE AF: 0.0172

Gnomad4 OTH AF: 0.0237

Alfa AF: 0.0159 Hom.: 8

Bravo AF: 0.0160

Asia WGS AF: 0.0520 AC: 181 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.1
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2287773; hg19: chr5-147443443;