NM_006846.4(SPINK5):c.1282A>G (p.Lys428Glu) AND Netherton syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 30, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000768323.2

Allele description [Variation Report for NM_006846.4(SPINK5):c.1282A>G (p.Lys428Glu)]

NM_006846.4(SPINK5):c.1282A>G (p.Lys428Glu)

Gene:

SPINK5:serine peptidase inhibitor Kazal type 5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q32

Genomic location:

Preferred name:

NM_006846.4(SPINK5):c.1282A>G (p.Lys428Glu)

HGVS:

NC_000005.10:g.148101416A>G
NG_009633.1:g.42445A>G
NM_001127698.2:c.1282A>G
NM_001127699.2:c.1282A>G
NM_006846.4:c.1282A>GMANE SELECT
NP_001121170.1:p.Lys428Glu
NP_001121171.1:p.Lys428Glu
NP_006837.2:p.Lys428Glu
LRG_110:g.42445A>G
NC_000005.9:g.147480979A>G

Protein change:

K428E

Links:

dbSNP: rs1428055248

NCBI 1000 Genomes Browser:

rs1428055248

Molecular consequence:

NM_001127698.2:c.1282A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127699.2:c.1282A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_006846.4:c.1282A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Netherton syndrome (NETH)
Synonyms:: Netherton disease; ERYTHRODERMA, ICHTHYOSIFORM, WITH HYPOTRICHOSIS AND HYPER-IgE; COMEL-NETHERTON SYNDROME
Identifiers:: MONDO: MONDO:0009735; MedGen: C5574950; Orphanet: 634; OMIM: 256500

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000898992	Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 30, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000898992

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 30, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago, SCV000898992.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

SPINK5 NM_006846.3 exon 14 p.Lys428Glu (c.1282A>G): This variant has not been reported in the literature but is present in 1/33494 Latino alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/5-147480979-A-G). This variant Glutamic acid (Glu) is present in several species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 27, 2023

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