rs2303068

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

11 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 260044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
SPINK5	NM_006846.4 link	c.1302+19G>A		intron_variant	Intron 14 of 32	ENST00000256084.8	NP_006837.2	Q9NQ38-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPINK5	ENST00000256084.8 link	c.1302+19G>A		intron_variant	Intron 14 of 32	1	NM_006846.4	ENSP00000256084.7		Q9NQ38-1

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

GnomAD2 exomes

AF:

0.520

AC:

128745

AN:

247788

AF XY:

0.518

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 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

African (AFR)

AF:

0.228

AC:

7476

AN:

32832

American (AMR)

AF:

0.684

AC:

30468

AN:

44518

Ashkenazi Jewish (ASJ)

AF:

0.460

AC:

11882

AN:

25810

East Asian (EAS)

AF:

0.446

AC:

17583

AN:

39446

South Asian (SAS)

AF:

0.488

AC:

41693

AN:

85404

European-Finnish (FIN)

AF:

0.549

AC:

29281

AN:

53332

Middle Eastern (MID)

AF:

0.507

AC:

2879

AN:

5680

European-Non Finnish (NFE)

AF:

0.517

AC:

555617

AN:

1073708

Other (OTH)

AF:

0.500

AC:

29501

AN:

59058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

16695

33391

50086

66782

83477

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15714

31428

47142

62856

78570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.447

AC:

67802

AN:

151588

Hom.:

16469

Cov.:

AF XY:

0.451

AC XY:

33388

AN XY:

73990

show subpopulations

African (AFR)

AF:

0.238

AC:

9827

AN:

41352

American (AMR)

AF:

0.581

AC:

8834

AN:

15206

Ashkenazi Jewish (ASJ)

AF:

0.454

AC:

1575

AN:

3468

East Asian (EAS)

AF:

0.475

AC:

2424

AN:

5098

South Asian (SAS)

AF:

0.491

AC:

2356

AN:

4796

European-Finnish (FIN)

AF:

0.537

AC:

5622

AN:

10472

Middle Eastern (MID)

AF:

0.490

AC:

141

AN:

288

European-Non Finnish (NFE)

AF:

0.524

AC:

35556

AN:

67892

Other (OTH)

AF:

0.477

AC:

1004

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1773

3545

5318

7090

8863

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

632

1264

1896

2528

3160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.472

Hom.:

4326

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

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Ichthyosis linearis circumflexa

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Netherton syndrome

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.12

(source)

DANN

Benign

0.22

PhyloP100

-0.33

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over