rs3764930

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001127698.2(SPINK5):c.2769G>A(p.Ala923Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 1,613,138 control chromosomes in the GnomAD database, including 292,662 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 22072 hom., cov: 32)

Exomes 𝑓: 0.60 ( 270590 hom. )

Consequence

SPINK5
NM_001127698.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.607

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 5-148125553-G-A is Benign according to our data. Variant chr5-148125553-G-A is described in ClinVar as [Benign]. Clinvar id is 403487.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-148125553-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.607 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPINK5	NM_006846.4 link	c.2740-170G>A		intron_variant	Intron 28 of 32	ENST00000256084.8	NP_006837.2	Q9NQ38-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPINK5	ENST00000359874.7 link	c.2769G>A	p.Ala923Ala	synonymous_variant	Exon 29 of 34	1		ENSP00000352936.3	Q9NQ38-3
SPINK5	ENST00000256084.8 link	c.2740-170G>A		intron_variant	Intron 28 of 32	1	NM_006846.4	ENSP00000256084.7	Q9NQ38-1
FBXO38-DT	ENST00000667608.1 link	n.1257-31811C>T		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes

AF:

0.512

AC:

77786

AN:

151840

Hom.:

22060

Cov.:

show subpopulations

Gnomad AFR

AF:

0.249

Gnomad AMI

AF:

0.592

Gnomad AMR

AF:

0.628

Gnomad ASJ

AF:

0.528

Gnomad EAS

AF:

0.472

Gnomad SAS

AF:

0.505

Gnomad FIN

AF:

0.633

Gnomad MID

AF:

0.542

Gnomad NFE

AF:

0.629

Gnomad OTH

AF:

0.520

GnomAD3 exomes

AF:

0.585

AC:

145413

AN:

248372

Hom.:

44392

AF XY:

0.583

AC XY:

78619

AN XY:

134886

show subpopulations

Gnomad AFR exome

AF:

0.244

Gnomad AMR exome

AF:

0.735

Gnomad ASJ exome

AF:

0.540

Gnomad EAS exome

AF:

0.461

Gnomad SAS exome

AF:

0.505

Gnomad FIN exome

AF:

0.642

Gnomad NFE exome

AF:

0.621

Gnomad OTH exome

AF:

0.590

GnomAD4 exome

AF:

0.603

AC:

881185

AN:

1461180

Hom.:

270590

Cov.:

AF XY:

0.601

AC XY:

436558

AN XY:

726850

show subpopulations

Gnomad4 AFR exome

AF:

0.233

Gnomad4 AMR exome

AF:

0.720

Gnomad4 ASJ exome

AF:

0.539

Gnomad4 EAS exome

AF:

0.438

Gnomad4 SAS exome

AF:

0.509

Gnomad4 FIN exome

AF:

0.642

Gnomad4 NFE exome

AF:

0.624

Gnomad4 OTH exome

AF:

0.577

GnomAD4 genome

AF:

0.512

AC:

77810

AN:

151958

Hom.:

22072

Cov.:

AF XY:

0.513

AC XY:

38112

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.249

Gnomad4 AMR

AF:

0.629

Gnomad4 ASJ

AF:

0.528

Gnomad4 EAS

AF:

0.471

Gnomad4 SAS

AF:

0.506

Gnomad4 FIN

AF:

0.633

Gnomad4 NFE

AF:

0.629

Gnomad4 OTH

AF:

0.521

Alfa

AF:

0.598

Hom.:

45188

Bravo

AF:

0.501

Asia WGS

AF:

0.522

AC:

1809

AN:

3478

EpiCase

AF:

0.616

EpiControl

AF:

0.615

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

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 91% of patients studied by a panel of primary immunodeficiencies. Number of patients: 80. Only high quality variants are reported. -

not provided

Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.25

DANN

Benign

0.51

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