rs11958432

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006846.4(SPINK5):c.882+20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 1,592,966 control chromosomes in the GnomAD database, including 207,603 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 17090 hom., cov: 31)

Exomes 𝑓: 0.51 ( 190513 hom. )

Consequence

SPINK5
NM_006846.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0110

Variant links:

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 links:

FBXO38-DT (HGNC:55589): (FBXO38 divergent transcript)

FBXO38-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 5-148095925-A-G is Benign according to our data. Variant chr5-148095925-A-G is described in ClinVar as [Benign]. Clinvar id is 260056.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-148095925-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPINK5	NM_006846.4 linkuse as main transcript	c.882+20A>G		intron_variant		ENST00000256084.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPINK5	ENST00000256084.8 linkuse as main transcript	c.882+20A>G		intron_variant		1	NM_006846.4	P2	Q9NQ38-1
FBXO38-DT	ENST00000667608.1 linkuse as main transcript	n.1257-2183T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.464

AC:

70330

AN:

151610

Hom.:

17084

Cov.:

show subpopulations

Gnomad AFR

AF:

0.307

Gnomad AMI

AF:

0.506

Gnomad AMR

AF:

0.589

Gnomad ASJ

AF:

0.449

Gnomad EAS

AF:

0.474

Gnomad SAS

AF:

0.489

Gnomad FIN

AF:

0.533

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.517

Gnomad OTH

AF:

0.489

GnomAD3 exomes

AF:

0.521

AC:

129019

AN:

247402

Hom.:

34735

AF XY:

0.518

AC XY:

69565

AN XY:

134308

show subpopulations

Gnomad AFR exome

AF:

0.310

Gnomad AMR exome

AF:

0.703

Gnomad ASJ exome

AF:

0.458

Gnomad EAS exome

AF:

0.477

Gnomad SAS exome

AF:

0.485

Gnomad FIN exome

AF:

0.546

Gnomad NFE exome

AF:

0.513

Gnomad OTH exome

AF:

0.523

GnomAD4 exome

AF:

0.510

AC:

735732

AN:

1441238

Hom.:

190513

Cov.:

AF XY:

0.509

AC XY:

365742

AN XY:

718252

show subpopulations

Gnomad4 AFR exome

AF:

0.299

Gnomad4 AMR exome

AF:

0.687

Gnomad4 ASJ exome

AF:

0.456

Gnomad4 EAS exome

AF:

0.450

Gnomad4 SAS exome

AF:

0.486

Gnomad4 FIN exome

AF:

0.545

Gnomad4 NFE exome

AF:

0.514

Gnomad4 OTH exome

AF:

0.502

GnomAD4 genome

AF:

0.464

AC:

70350

AN:

151728

Hom.:

17090

Cov.:

AF XY:

0.467

AC XY:

34635

AN XY:

74128

show subpopulations

Gnomad4 AFR

AF:

0.307

Gnomad4 AMR

AF:

0.590

Gnomad4 ASJ

AF:

0.449

Gnomad4 EAS

AF:

0.473

Gnomad4 SAS

AF:

0.490

Gnomad4 FIN

AF:

0.533

Gnomad4 NFE

AF:

0.517

Gnomad4 OTH

AF:

0.490

Alfa

AF:

0.474

Hom.:

3568

Bravo

AF:

0.466

Asia WGS

AF:

0.520

AC:

1804

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 88% of patients studied by a panel of primary immunodeficiencies. Number of patients: 84. Only high quality variants are reported. -

Ichthyosis linearis circumflexa

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Netherton syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

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

-0.88

Cadd

Benign

1.5

Dann

Benign

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over