NM_006846.4(SPINK5):c.1216TTC[1] (p.Phe407del) AND Netherton syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 16, 2022
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:: RCV001366101.8

Allele description [Variation Report for NM_006846.4(SPINK5):c.1216TTC[1] (p.Phe407del)]

NM_006846.4(SPINK5):c.1216TTC[1] (p.Phe407del)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

5q32

Genomic location:

Preferred name:

NM_006846.4(SPINK5):c.1216TTC[1] (p.Phe407del)

HGVS:

NC_000005.10:g.148100576CTT[1]
NG_009633.1:g.41605CTT[1]
NM_001127698.2:c.1216TTC[1]
NM_001127699.2:c.1216TTC[1]
NM_006846.4:c.1216TTC[1]MANE SELECT
NP_001121170.1:p.Phe407del
NP_001121171.1:p.Phe407del
NP_006837.2:p.Phe407del
LRG_110:g.41605CTT[1]
NC_000005.9:g.147480138_147480140del
NC_000005.9:g.147480139CTT[1]

Protein change:

F407del

Links:

dbSNP: rs2113117124

NCBI 1000 Genomes Browser:

rs2113117124

Molecular consequence:

NM_001127698.2:c.1216TTC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001127699.2:c.1216TTC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_006846.4:c.1216TTC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]

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
SCV001562392	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 16, 2022)	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

SCV001562392

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 16, 2022)

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001562392.4

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

Description

This variant, c.1218_1220del, results in the deletion of 1 amino acid(s) of the SPINK5 protein (p.Phe407del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SPINK5-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Sep 29, 2024

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