17-61480239-C-T

Position:

chr17-61480239-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001321120.2(TBX4):c.941C>T(p.Ala314Val) variant causes a missense change. The variant allele was found at a frequency of 0.131 in 1,613,842 control chromosomes in the GnomAD database, including 17,444 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 4427 hom., cov: 32)

Exomes 𝑓: 0.12 ( 13017 hom. )

Consequence

TBX4
NM_001321120.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 4.57

Variant links:

Genes affected

TBX4 (HGNC:11603): (T-box transcription factor 4) 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 is the human homolog of mouse Tbx4, which is closely linked to Tbx2 on mouse chromosome 11. Similarly this gene, like TBX2, maps to human chromosome 17. Expression studies in mouse and chicken show that Tbx4 is expressed in developing hindlimb, but not in forelimb buds, suggesting a role for this gene in regulating limb development and specification of limb identity. [provided by RefSeq, Jul 2008]

TBX4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005241424).

BP6

Variant 17-61480239-C-T is Benign according to our data. Variant chr17-61480239-C-T is described in ClinVar as [Benign]. Clinvar id is 261035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-61480239-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBX4	NM_001321120.2 linkuse as main transcript	c.941C>T	p.Ala314Val	missense_variant	8/9	ENST00000644296.1	NP_001308049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBX4	ENST00000644296.1 linkuse as main transcript	c.941C>T	p.Ala314Val	missense_variant	8/9		NM_001321120.2	ENSP00000495986	A1	P57082-2

Frequencies

GnomAD3 genomes

AF:

0.202

AC:

30625

AN:

151898

Hom.:

4406

Cov.:

show subpopulations

Gnomad AFR

AF:

0.404

Gnomad AMI

AF:

0.115

Gnomad AMR

AF:

0.163

Gnomad ASJ

AF:

0.201

Gnomad EAS

AF:

0.108

Gnomad SAS

AF:

0.143

Gnomad FIN

AF:

0.0872

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.118

Gnomad OTH

AF:

0.192

GnomAD3 exomes

AF:

0.139

AC:

34792

AN:

250082

Hom.:

3188

AF XY:

0.135

AC XY:

18309

AN XY:

135354

show subpopulations

Gnomad AFR exome

AF:

0.419

Gnomad AMR exome

AF:

0.114

Gnomad ASJ exome

AF:

0.199

Gnomad EAS exome

AF:

0.108

Gnomad SAS exome

AF:

0.130

Gnomad FIN exome

AF:

0.0863

Gnomad NFE exome

AF:

0.119

Gnomad OTH exome

AF:

0.141

GnomAD4 exome

AF:

0.124

AC:

180782

AN:

1461826

Hom.:

13017

Cov.:

AF XY:

0.124

AC XY:

89878

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.409

Gnomad4 AMR exome

AF:

0.120

Gnomad4 ASJ exome

AF:

0.196

Gnomad4 EAS exome

AF:

0.114

Gnomad4 SAS exome

AF:

0.130

Gnomad4 FIN exome

AF:

0.0877

Gnomad4 NFE exome

AF:

0.114

Gnomad4 OTH exome

AF:

0.145

GnomAD4 genome

AF:

0.202

AC:

30687

AN:

152016

Hom.:

4427

Cov.:

AF XY:

0.199

AC XY:

14761

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.404

Gnomad4 AMR

AF:

0.162

Gnomad4 ASJ

AF:

0.201

Gnomad4 EAS

AF:

0.108

Gnomad4 SAS

AF:

0.142

Gnomad4 FIN

AF:

0.0872

Gnomad4 NFE

AF:

0.118

Gnomad4 OTH

AF:

0.194

Alfa

AF:

0.142

Hom.:

3038

Bravo

AF:

0.215

TwinsUK

AF:

0.108

AC:

399

ALSPAC

AF:

0.116

AC:

448

ESP6500AA

AF:

0.414

AC:

1822

ESP6500EA

AF:

0.124

AC:

1070

ExAC

AF:

0.145

AC:

17594

Asia WGS

AF:

0.168

AC:

581

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 01, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Coxopodopatellar syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.062

.;.;T;.

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.38

.;.;T;T

MetaRNN

Benign

0.0052

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L;L;L

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.40

N;.;N;.

REVEL

Benign

0.26

Sift

Benign

0.035

D;.;D;.

Sift4G

Benign

0.24

T;.;T;.

Polyphen

0.85

.;.;P;.

Vest4

0.17

MPC

0.59

ClinPred

0.028

GERP RS

5.8

Varity_R

0.13

gMVP

0.15

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