NM_003809.3(TNFSF12):c.64G>C (p.Val22Leu) AND Common variable immunodeficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 11, 2018
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:: RCV000814247.6

Allele description [Variation Report for NM_003809.3(TNFSF12):c.64G>C (p.Val22Leu)]

NM_003809.3(TNFSF12):c.64G>C (p.Val22Leu)

Genes:

LOC130060153:ATAC-STARR-seq lymphoblastoid silent region 8127 [Gene]
TNFSF12:TNF superfamily member 12 [Gene - OMIM - HGNC]
TNFSF12-TNFSF13:TNFSF12-TNFSF13 readthrough [Gene - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_003809.3(TNFSF12):c.64G>C (p.Val22Leu)

HGVS:

NC_000017.11:g.7549217G>C
NG_052944.1:g.5160G>C
NM_003809.3:c.64G>CMANE SELECT
NM_172089.4:c.64G>C
NP_003800.1:p.Val22Leu
NP_742086.1:p.Val22Leu
LRG_1320t1:c.64G>C
LRG_1320:g.5160G>C
LRG_1320p1:p.Val22Leu
NC_000017.10:g.7452534G>C
NM_003809.2:c.64G>C
NR_037146.2:n.160G>C

Protein change:

V22L

Links:

dbSNP: rs1413049593

NCBI 1000 Genomes Browser:

rs1413049593

Molecular consequence:

NM_003809.3:c.64G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_172089.4:c.64G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_037146.2:n.160G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Common variable immunodeficiency (CVID)
Synonyms:: Common variable hypogamma-globulinemia; Common variable agammaglobulinemia
Identifiers:: MONDO: MONDO:0015517; MedGen: C0009447; Orphanet: 1572; OMIM: PS607594

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000954649	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 11, 2018)	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

SCV000954649

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 11, 2018)

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000954649.4

#	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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with TNFSF12-related disease. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces valine with leucine at codon 22 of the TNFSF12 protein (p.Val22Leu). The valine residue is weakly conserved and there is a small physicochemical difference between valine and leucine.

#	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: Feb 20, 2024

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