NM_001379200.1:c.1086A>G

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001379200.1(TBX1):c.1086A>G(p.Ala362Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0686 in 1,343,886 control chromosomes in the GnomAD database, including 3,899 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.093 ( 926 hom., cov: 33)

Exomes 𝑓: 0.065 ( 2973 hom. )

Consequence

TBX1
NM_001379200.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.53

Variant links:

Genes affected

TBX1 (HGNC:11592): (T-box transcription factor 1) This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. This gene product shares 98% amino acid sequence identity with the mouse ortholog. DiGeorge syndrome (DGS)/velocardiofacial syndrome (VCFS), a common congenital disorder characterized by neural-crest-related developmental defects, has been associated with deletions of chromosome 22q11.2, where this gene has been mapped. Studies using mouse models of DiGeorge syndrome suggest a major role for this gene in the molecular etiology of DGS/VCFS. Several alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

TBX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 22-19766438-A-G is Benign according to our data. Variant chr22-19766438-A-G is described in ClinVar as [Benign]. Clinvar id is 263355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-19766438-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.53 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX1	NM_001379200.1 link	c.1086A>G	p.Ala362Ala	synonymous_variant	Exon 7 of 7	ENST00000649276.2	NP_001366129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBX1	ENST00000649276.2 link	c.1086A>G	p.Ala362Ala	synonymous_variant	Exon 7 of 7		NM_001379200.1	ENSP00000497003.1		A0A3B3IS18

Frequencies

GnomAD3 genomes

AF:

0.0933

AC:

14080

AN:

150968

Hom.:

925

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.0622

Gnomad ASJ

AF:

0.0570

Gnomad EAS

AF:

0.000586

Gnomad SAS

AF:

0.0156

Gnomad FIN

AF:

0.0311

Gnomad MID

AF:

0.0784

Gnomad NFE

AF:

0.0673

Gnomad OTH

AF:

0.0829

GnomAD3 exomes

AF:

0.0480

AC:

1827

AN:

38034

Hom.:

AF XY:

0.0449

AC XY:

1014

AN XY:

22580

show subpopulations

Gnomad AFR exome

AF:

0.190

Gnomad AMR exome

AF:

0.0399

Gnomad ASJ exome

AF:

0.0594

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0222

Gnomad FIN exome

AF:

0.0291

Gnomad NFE exome

AF:

0.0655

Gnomad OTH exome

AF:

0.0593

GnomAD4 exome

AF:

0.0655

AC:

78102

AN:

1192808

Hom.:

2973

Cov.:

AF XY:

0.0638

AC XY:

37286

AN XY:

584386

show subpopulations

Gnomad4 AFR exome

AF:

0.196

Gnomad4 AMR exome

AF:

0.0496

Gnomad4 ASJ exome

AF:

0.0581

Gnomad4 EAS exome

AF:

0.000155

Gnomad4 SAS exome

AF:

0.0209

Gnomad4 FIN exome

AF:

0.0353

Gnomad4 NFE exome

AF:

0.0675

Gnomad4 OTH exome

AF:

0.0694

GnomAD4 genome

AF:

0.0932

AC:

14085

AN:

151078

Hom.:

926

Cov.:

AF XY:

0.0891

AC XY:

6582

AN XY:

73846

show subpopulations

Gnomad4 AFR

AF:

0.187

Gnomad4 AMR

AF:

0.0621

Gnomad4 ASJ

AF:

0.0570

Gnomad4 EAS

AF:

0.000588

Gnomad4 SAS

AF:

0.0154

Gnomad4 FIN

AF:

0.0311

Gnomad4 NFE

AF:

0.0672

Gnomad4 OTH

AF:

0.0821

Alfa

AF:

0.0838

Hom.:

Bravo

AF:

0.0991

Asia WGS

AF:

0.0190

AC:

AN:

3382

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apr 10, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

DiGeorge syndrome

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiovascular phenotype

Benign:1

Jul 15, 2015

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.9

DANN

Benign

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over