rs2303068

chr5-148101455-G-Achr5-148101455-G-Cchr5-148101455-G-T

Variant summary

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

The NM_006846.4(SPINK5):c.1302+19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 1,571,376 control chromosomes in the GnomAD database, including 205,470 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 16469 hom., cov: 31)

Exomes 𝑓: 0.51 ( 189001 hom. )

Consequence

SPINK5
NM_006846.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.326

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=-0.92).

BP6

Variant 5-148101455-G-A is Benign according to our data. Variant chr5-148101455-G-A is described in ClinVar as [Benign]. Clinvar id is 260044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-148101455-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.571 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.1302+19G>A		intron_variant		ENST00000256084.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPINK5	ENST00000256084.8 linkuse as main transcript	c.1302+19G>A		intron_variant		1	NM_006846.4	P2	Q9NQ38-1
FBXO38-DT	ENST00000667608.1 linkuse as main transcript	n.1257-7713C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.447

AC:

67780

AN:

151470

Hom.:

16459

Cov.:

show subpopulations

Gnomad AFR

AF:

0.238

Gnomad AMI

AF:

0.509

Gnomad AMR

AF:

0.581

Gnomad ASJ

AF:

0.454

Gnomad EAS

AF:

0.476

Gnomad SAS

AF:

0.490

Gnomad FIN

AF:

0.537

Gnomad MID

AF:

0.510

Gnomad NFE

AF:

0.524

Gnomad OTH

AF:

0.474

GnomAD3 exomes

AF:

0.520

AC:

128745

AN:

247788

Hom.:

34841

AF XY:

0.518

AC XY:

69557

AN XY:

134372

show subpopulations

Gnomad AFR exome

AF:

0.237

Gnomad AMR exome

AF:

0.700

Gnomad ASJ exome

AF:

0.462

Gnomad EAS exome

AF:

0.473

Gnomad SAS exome

AF:

0.487

Gnomad FIN exome

AF:

0.550

Gnomad NFE exome

AF:

0.519

Gnomad OTH exome

AF:

0.524

GnomAD4 exome

AF:

0.512

AC:

726380

AN:

1419788

Hom.:

189001

Cov.:

AF XY:

0.511

AC XY:

362251

AN XY:

708960

show subpopulations

Gnomad4 AFR exome

AF:

0.228

Gnomad4 AMR exome

AF:

0.684

Gnomad4 ASJ exome

AF:

0.460

Gnomad4 EAS exome

AF:

0.446

Gnomad4 SAS exome

AF:

0.488

Gnomad4 FIN exome

AF:

0.549

Gnomad4 NFE exome

AF:

0.517

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

AF:

0.447

AC:

67802

AN:

151588

Hom.:

16469

Cov.:

AF XY:

0.451

AC XY:

33388

AN XY:

73990

show subpopulations

Gnomad4 AFR

AF:

0.238

Gnomad4 AMR

AF:

0.581

Gnomad4 ASJ

AF:

0.454

Gnomad4 EAS

AF:

0.475

Gnomad4 SAS

AF:

0.491

Gnomad4 FIN

AF:

0.537

Gnomad4 NFE

AF:

0.524

Gnomad4 OTH

AF:

0.477

Alfa

AF:

0.477

Hom.:

4303

Bravo

AF:

0.445

Asia WGS

AF:

0.520

AC:

1803

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	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 89% of patients studied by a panel of primary immunodeficiencies. Number of patients: 78. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

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

-0.92

Cadd

Benign

0.12

Dann

Benign

0.22

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

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