NM_001379200.1(TBX1):c.1484C>A (p.Pro495Gln) AND DiGeorge syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 5, 2023
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:: RCV001248343.8

Allele description [Variation Report for NM_001379200.1(TBX1):c.1484C>A (p.Pro495Gln)]

NM_001379200.1(TBX1):c.1484C>A (p.Pro495Gln)

Gene:

TBX1:T-box transcription factor 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q11.21

Genomic location:

Preferred name:

NM_001379200.1(TBX1):c.1484C>A (p.Pro495Gln)

HGVS:

NC_000022.11:g.19766836C>A
NG_009229.1:g.15134C>A
NM_001379200.1:c.1484C>AMANE SELECT
NM_005992.1:c.1009+834C>A
NM_080646.2:c.1009+834C>A
NM_080647.1:c.1457C>A
NP_001366129.1:p.Pro495Gln
NP_542378.1:p.Pro486Gln
LRG_226t1:c.1457C>A
LRG_226:g.15134C>A
LRG_226p1:p.Pro486Gln
NC_000022.10:g.19754359C>A

Protein change:

P486Q

Links:

dbSNP: rs762076391

NCBI 1000 Genomes Browser:

rs762076391

Molecular consequence:

NM_005992.1:c.1009+834C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_080646.2:c.1009+834C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001379200.1:c.1484C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_080647.1:c.1457C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: DiGeorge syndrome
Synonyms:: Hypoplasia of thymus and parathyroid; Third and fourth pharyngeal pouch syndrome; DiGeorge anomaly; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008564; MedGen: C0012236; Orphanet: 567; OMIM: 188400

Recent activity

Clear Turn Off Turn On

AMT [Cercocebus atys]
AMT [Cercocebus atys]
Gene ID:105573692

Gene

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001421819	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 5, 2023)	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

SCV001421819

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 5, 2023)

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, SCV001421819.6

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

Description

This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 486 of the TBX1 protein (p.Pro486Gln). This variant is present in population databases (rs762076391, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with TBX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 586784). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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

ClinVar

Relating variation to medicine