NM_003998.4(NFKB1):c.322C>T (p.His108Tyr) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 1, 2022
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:: RCV001327030.7

Allele description

NM_003998.4(NFKB1):c.322C>T (p.His108Tyr)

Gene:

NFKB1:nuclear factor kappa B subunit 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4q24

Genomic location:

Preferred name:

NM_003998.4(NFKB1):c.322C>T (p.His108Tyr)

HGVS:

NC_000004.12:g.102567050C>T
NG_050628.1:g.70722C>T
NM_001165412.2:c.319C>T
NM_001319226.2:c.319C>T
NM_001382625.1:c.322C>T
NM_001382626.1:c.322C>T
NM_001382627.1:c.319C>T
NM_001382628.1:c.280C>T
NM_003998.4:c.322C>TMANE SELECT
NP_001158884.1:p.His107Tyr
NP_001306155.1:p.His107Tyr
NP_001369554.1:p.His108Tyr
NP_001369555.1:p.His108Tyr
NP_001369556.1:p.His107Tyr
NP_001369557.1:p.His94Tyr
NP_003989.2:p.His108Tyr
LRG_1316t1:c.322C>T
LRG_1316:g.70722C>T
LRG_1316p1:p.His108Tyr
NC_000004.11:g.103488207C>T

Protein change:

H107Y

Links:

dbSNP: rs749065614

NCBI 1000 Genomes Browser:

rs749065614

Molecular consequence:

NM_001165412.2:c.319C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001319226.2:c.319C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382625.1:c.322C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382626.1:c.322C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382627.1:c.319C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001382628.1:c.280C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003998.4:c.322C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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
SCV001518088	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 14, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004153025	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (Mar 1, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001518088

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 14, 2022)

germline

clinical testing

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

SCV004153025

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Uncertain significance
(Mar 1, 2022)

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	1	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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001518088.3

#	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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 1026562). This variant has not been reported in the literature in individuals affected with NFKB1-related conditions. This variant is present in population databases (rs749065614, gnomAD 0.002%). This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 108 of the NFKB1 protein (p.His108Tyr).

#	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 CeGaT Center for Human Genetics Tuebingen, SCV004153025.4

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

Description

NFKB1: PM2

#	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		1	not provided	not provided	not provided

Last Updated: Apr 15, 2024

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