VCV003340541.1 - ClinVar

NM_015331.3(NCSTN):c.344_351del (p.Thr115fs)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Uncertain significance

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_015331.3(NCSTN):c.344_351del (p.Thr115fs)

Variation ID: 3340541 Accession: VCV003340541.1

Type and length

Deletion, 8 bp

Location

Cytogenetic: 1q23.2 1: 160349577-160349584 (GRCh38) [ NCBI UCSC ] 1: 160319367-160319374 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Oct 8, 2024	Oct 8, 2024	Sep 23, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_015331.3:c.344_351del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_056146.1:p.Thr115fs	frameshift
NM_001290184.2:c.284_291del	NP_001277113.1:p.Thr95fs	frameshift
NM_001290186.2:c.344_351del	NP_001277115.1:p.Thr115fs	frameshift
NM_001349729.2:c.344_351del	NP_001336658.1:p.Thr115fs	frameshift
NC_000001.11:g.160349578_160349585del
NC_000001.10:g.160319368_160319375del
NG_027935.1:g.11306_11313del
LRG_223:g.11306_11313del
LRG_223t1:c.344_351del	LRG_223p1:p.Thr115fs
LRG_223t2:c.284_291del	LRG_223p2:p.Thr95fs

... more HGVS ... less HGVS

Protein change

T115fs, T95fs

Other names

Canonical SPDI

NC_000001.11:160349576:ACCAGCCGA:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

OMIM: 605254.0007 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
NCSTN		-	-	GRCh38 GRCh37	422	435

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not provided	Uncertain significance (1)	no assertion criteria provided	Sep 23, 2024	RCV004721825.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Uncertain significance (Sep 23, 2024)	no assertion criteria provided Method: literature only	VARIANT OF UNKNOWN SIGNIFICANCE Affected status: not provided Allele origin: germline	OMIM Accession: SCV005326569.1 First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024	Publications: PubMed (1) PubMed: 25601011 Comment on evidence: This variant is classified as a variant of unknown significance because its contribution to pyoderma gangrenosum, acne, and hidradenitis suppurativa, also known as PASH syndrome … (more) This variant is classified as a variant of unknown significance because its contribution to pyoderma gangrenosum, acne, and hidradenitis suppurativa, also known as PASH syndrome (see 604416), has not been confirmed. In a 29-year-old woman (patient 3) with severe hidradenitis suppurative from age 11 years, followed by severe acne and extensive pyoderma gangrenosum of the trunk and limbs, Duchatelet et al. (2015) sequenced the PSTPIP1 (606347) promoter and gene, and the candidate genes NCSTN, PSENEN (607632), and PSEN1 (104311), and identified heterozygosity for an 8-bp deletion (c.344_351del, NM_015331.2) in the NCSTN gene, causing a frameshift predicted to result in a premature termination codon (Thr115AsnTer20). Because the patient was adopted, familial segregation could not be analyzed; the variant was not found in 434 in-house exomes or in 6,503 individuals from the NHLBI Exome Sequencing Project database. The authors noted that patient 3 was also heterozygous for increased CCTG repeats in the PSTPIP1 promoter region, but stated that there was no evidence that this variation had any functional effect. (less)

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
First nicastrin mutation in PASH (pyoderma gangrenosum, acne and suppurative hidradenitis) syndrome.	Duchatelet S	The British journal of dermatology	2015	PMID: 25601011

Text-mined citations for this variant ...

Record last updated Oct 08, 2024

ClinVar Genomic variation as it relates to human health

NM_015331.3(NCSTN):c.344_351del (p.Thr115fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...