rs41298840

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.960A>G(p.Ala320Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,527,280 control chromosomes in the GnomAD database, including 39,847 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3524 hom., cov: 33)

Exomes 𝑓: 0.22 ( 36323 hom. )

Consequence

TBX1
NM_001379200.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.830

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=-0.76).

BP6

Variant 22-19765926-A-G is Benign according to our data. Variant chr22-19765926-A-G is described in ClinVar as [Benign]. Clinvar id is 263444.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-19765926-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.83 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX1	NM_001379200.1 link	c.960A>G	p.Ala320Ala	synonymous_variant	Exon 6 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.960A>G	p.Ala320Ala	synonymous_variant	Exon 6 of 7		NM_001379200.1	ENSP00000497003.1		A0A3B3IS18

Frequencies

GnomAD3 genomes

AF:

0.186

AC:

28121

AN:

151480

Hom.:

3527

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0457

Gnomad AMI

AF:

0.221

Gnomad AMR

AF:

0.270

Gnomad ASJ

AF:

0.321

Gnomad EAS

AF:

0.484

Gnomad SAS

AF:

0.239

Gnomad FIN

AF:

0.156

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.222

Gnomad OTH

AF:

0.205

GnomAD3 exomes

AF:

0.230

AC:

28609

AN:

124464

Hom.:

3906

AF XY:

0.229

AC XY:

15549

AN XY:

67972

show subpopulations

Gnomad AFR exome

AF:

0.0208

Gnomad AMR exome

AF:

0.300

Gnomad ASJ exome

AF:

0.287

Gnomad EAS exome

AF:

0.425

Gnomad SAS exome

AF:

0.213

Gnomad FIN exome

AF:

0.159

Gnomad NFE exome

AF:

0.204

Gnomad OTH exome

AF:

0.207

GnomAD4 exome

AF:

0.221

AC:

304257

AN:

1375688

Hom.:

36323

Cov.:

AF XY:

0.222

AC XY:

150769

AN XY:

678254

show subpopulations

Gnomad4 AFR exome

AF:

0.0340

Gnomad4 AMR exome

AF:

0.297

Gnomad4 ASJ exome

AF:

0.304

Gnomad4 EAS exome

AF:

0.460

Gnomad4 SAS exome

AF:

0.226

Gnomad4 FIN exome

AF:

0.162

Gnomad4 NFE exome

AF:

0.217

Gnomad4 OTH exome

AF:

0.219

GnomAD4 genome

AF:

0.185

AC:

28114

AN:

151592

Hom.:

3524

Cov.:

AF XY:

0.188

AC XY:

13919

AN XY:

74074

show subpopulations

Gnomad4 AFR

AF:

0.0456

Gnomad4 AMR

AF:

0.271

Gnomad4 ASJ

AF:

0.321

Gnomad4 EAS

AF:

0.483

Gnomad4 SAS

AF:

0.238

Gnomad4 FIN

AF:

0.156

Gnomad4 NFE

AF:

0.222

Gnomad4 OTH

AF:

0.202

Alfa

AF:

0.213

Hom.:

808

Bravo

AF:

0.187

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Apr 04, 2023

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Dec 16, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:3

May 07, 2018

Athena Diagnostics

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

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

DiGeorge syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiovascular phenotype

Benign:1

Jun 12, 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

-0.76

CADD

Benign

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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