Variant 5-148088671-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006846.4(SPINK5):c.474+66C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 1,488,210 control chromosomes in the GnomAD database, including 194,987 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 17128 hom., cov: 30)

Exomes 𝑓: 0.51 ( 177859 hom. )

Consequence

SPINK5
NM_006846.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.75

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:

SPINK5 (HGNC:):

SPINK5 links:

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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 5-148088671-C-G is Benign according to our data. Variant chr5-148088671-C-G is described in ClinVar as [Benign]. Clinvar id is 1222588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPINK5	NM_006846.4 linkuse as main transcript	c.474+66C>G		intron_variant		ENST00000256084.8	NP_006837.2	Q9NQ38-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPINK5	ENST00000256084.8 linkuse as main transcript	c.474+66C>G		intron_variant		1	NM_006846.4	ENSP00000256084.7		Q9NQ38-1

Frequencies

GnomAD3 genomes

AF:

0.466

AC:

70426

AN:

151158

Hom.:

17125

Cov.:

show subpopulations

Gnomad AFR

AF:

0.311

Gnomad AMI

AF:

0.507

Gnomad AMR

AF:

0.594

Gnomad ASJ

AF:

0.493

Gnomad EAS

AF:

0.495

Gnomad SAS

AF:

0.497

Gnomad FIN

AF:

0.534

Gnomad MID

AF:

0.538

Gnomad NFE

AF:

0.513

Gnomad OTH

AF:

0.499

GnomAD4 exome

AF:

0.513

AC:

686063

AN:

1336934

Hom.:

177859

AF XY:

0.512

AC XY:

343305

AN XY:

670944

show subpopulations

Gnomad4 AFR exome

AF:

0.307

Gnomad4 AMR exome

AF:

0.687

Gnomad4 ASJ exome

AF:

0.503

Gnomad4 EAS exome

AF:

0.477

Gnomad4 SAS exome

AF:

0.493

Gnomad4 FIN exome

AF:

0.545

Gnomad4 NFE exome

AF:

0.514

Gnomad4 OTH exome

AF:

0.509

GnomAD4 genome

AF:

0.466

AC:

70438

AN:

151276

Hom.:

17128

Cov.:

AF XY:

0.471

AC XY:

34769

AN XY:

73874

show subpopulations

Gnomad4 AFR

AF:

0.310

Gnomad4 AMR

AF:

0.594

Gnomad4 ASJ

AF:

0.493

Gnomad4 EAS

AF:

0.494

Gnomad4 SAS

AF:

0.498

Gnomad4 FIN

AF:

0.534

Gnomad4 NFE

AF:

0.513

Gnomad4 OTH

AF:

0.499

Alfa

AF:

0.462

Hom.:

2032

Bravo

AF:

0.466

Asia WGS

AF:

0.531

AC:

1842

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

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. -

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

0.29

DANN

Benign

0.69

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