NM_015559.3(SETBP1):c.869C>T (p.Ala290Val) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Feb 22, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV002658827.4

Allele description [Variation Report for NM_015559.3(SETBP1):c.869C>T (p.Ala290Val)]

NM_015559.3(SETBP1):c.869C>T (p.Ala290Val)

Gene:

SETBP1:SET binding protein 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18q12.3

Genomic location:

Preferred name:

NM_015559.3(SETBP1):c.869C>T (p.Ala290Val)

HGVS:

NC_000018.10:g.44950209C>T
NG_027527.2:g.275037C>T
NM_001379141.1:c.869C>T
NM_001379142.1:c.869C>T
NM_001410862.1:c.869C>T
NM_015559.2:c.869C>T
NM_015559.3:c.869C>TMANE SELECT
NP_001366070.1:p.Ala290Val
NP_001366071.1:p.Ala290Val
NP_001397791.1:p.Ala290Val
NP_056374.2:p.Ala290Val
LRG_1150t1:c.869C>T
LRG_1150:g.275037C>T
LRG_1150p1:p.Ala290Val
NC_000018.9:g.42530174C>T

Protein change:

A290V

Molecular consequence:

NM_001379141.1:c.869C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379142.1:c.869C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001410862.1:c.869C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_015559.3:c.869C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002985932	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 20, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004030723	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Feb 22, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002985932

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 20, 2022)

germline

clinical testing

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

SCV004030723

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Feb 22, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
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, SCV002985932.2

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with SETBP1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 290 of the SETBP1 protein (p.Ala290Val).

#	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

From GeneDx, SCV004030723.1

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

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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

Last Updated: Sep 29, 2024

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