5-148065222-A-G

Position:

• chr5-148065222-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000256084.8(SPINK5):​c.56-125A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 983,056 control chromosomes in the GnomAD database, including 186,667 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.60 (27343 hom., cov: 32)
  • Exomes 𝑓: 0.61 (159324 hom.)
• Consequence: SPINK5 ENST00000256084.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.618

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 5-148065222-A-G is Benign according to our data. Variant chr5-148065222-A-G is described in ClinVar as [Benign]. Clinvar id is 1274357.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPINK5	NM_006846.4	c.56-125A>G		intron_variant		ENST00000256084.8	NP_006837.2
SPINK5	NM_001127698.2	c.56-125A>G		intron_variant			NP_001121170.1
SPINK5	NM_001127699.2	c.56-125A>G		intron_variant			NP_001121171.1
SPINK5	XM_047416662.1	c.56-125A>G		intron_variant			XP_047272618.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPINK5	ENST00000256084.8	c.56-125A>G		intron_variant		1	NM_006846.4	ENSP00000256084.7

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90505 AN: 151854 Hom.: 27347 Cov.: 32

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.630

GnomAD4 exome AF: 0.613 AC: 509579 AN: 831084 Hom.: 159324 AF XY: 0.620 AC XY: 266860 AN XY: 430360

Gnomad4 AFR exome AF: 0.505

Gnomad4 AMR exome AF: 0.743

Gnomad4 ASJ exome AF: 0.640

Gnomad4 EAS exome AF: 0.743

Gnomad4 SAS exome AF: 0.779

Gnomad4 FIN exome AF: 0.636

Gnomad4 NFE exome AF: 0.580

Gnomad4 OTH exome AF: 0.620

GnomAD4 genome AF: 0.596 AC: 90528 AN: 151972 Hom.: 27343 Cov.: 32 AF XY: 0.604 AC XY: 44861 AN XY: 74262

Gnomad4 AFR AF: 0.513

Gnomad4 AMR AF: 0.672

Gnomad4 ASJ AF: 0.630

Gnomad4 EAS AF: 0.787

Gnomad4 SAS AF: 0.787

Gnomad4 FIN AF: 0.625

Gnomad4 NFE AF: 0.594

Gnomad4 OTH AF: 0.634

Alfa AF: 0.574 Hom.: 3169

Bravo AF: 0.597

Asia WGS AF: 0.773 AC: 2680 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.64
DANN	Benign	0.56

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: rs2287772; hg19: chr5-147444785;