rs201217462

Positions:

chr7-35202443-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_001077653.2(TBX20):c.1331C>T(p.Thr444Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,559,766 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

TBX20
NM_001077653.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 9.60

Variant links:

Genes affected

TBX20 (HGNC:11598): (T-box transcription factor 20) This gene encodes a T-box family member. The T-box family members share a common DNA binding domain, termed the T-box, and they are transcription factors involved in the regulation of developmental processes. This gene is essential for heart development. Mutations in this gene are associated with diverse cardiac pathologies, including defects in septation, valvulogenesis and cardiomyopathy. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

TBX20 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6

Variant 7-35202443-G-A is Benign according to our data. Variant chr7-35202443-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 519187.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.

BS2

High AC in GnomAd4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBX20	NM_001077653.2 linkuse as main transcript	c.1331C>T	p.Thr444Met	missense_variant	8/8	ENST00000408931.4	NP_001071121.1	Q9UMR3
TBX20	XM_017012456.2 linkuse as main transcript	c.734C>T	p.Thr245Met	missense_variant	6/6		XP_016867945.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBX20	ENST00000408931.4 linkuse as main transcript	c.1331C>T	p.Thr444Met	missense_variant	8/8	1	NM_001077653.2	ENSP00000386170.3		Q9UMR3

Frequencies

GnomAD3 genomes

AF:

0.0000865

AC:

AN:

150352

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000979

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000664

Gnomad ASJ

AF:

0.00116

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000591

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000109

AC:

AN:

229982

Hom.:

AF XY:

0.0000886

AC XY:

AN XY:

124166

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000919

Gnomad ASJ exome

AF:

0.00124

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000872

Gnomad OTH exome

AF:

0.000175

GnomAD4 exome

AF:

0.000121

AC:

171

AN:

1409292

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

698988

show subpopulations

Gnomad4 AFR exome

AF:

0.0000628

Gnomad4 AMR exome

AF:

0.000120

Gnomad4 ASJ exome

AF:

0.00123

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000239

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000109

Gnomad4 OTH exome

AF:

0.000245

GnomAD4 genome

AF:

0.0000864

AC:

AN:

150474

Hom.:

Cov.:

AF XY:

0.0000817

AC XY:

AN XY:

73434

show subpopulations

Gnomad4 AFR

AF:

0.0000976

Gnomad4 AMR

AF:

0.0000663

Gnomad4 ASJ

AF:

0.00116

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000591

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000225

Hom.:

Bravo

AF:

0.0000982

ESP6500AA

AF:

0.000262

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000745

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 07, 2023	- -
Uncertain significance, criteria provided, single submitter	clinical testing	GeneDx	Apr 07, 2021	Reported as a single nucleotide polymorphism (SNP) in an individual with an atrial septal defect (Monroy-Munoz et al., 2015); Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 519187; Landrum et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25834824) -

Cardiovascular phenotype

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 09, 2023

This alteration is classified as likely 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

AlphaMissense

Pathogenic

0.61

BayesDel_addAF

Uncertain

0.080

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.26

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

M_CAP

Uncertain

0.23

MetaRNN

Uncertain

0.61

MetaSVM

Uncertain

0.59

MutationAssessor

Benign

0.55

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.47

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0070

Polyphen

1.0

Vest4

0.84

MVP

0.87

MPC

1.5

ClinPred

0.23

GERP RS

5.7

Varity_R

0.26

gMVP

0.46

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