Variant 16-30091839-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The ENST00000553607.1(TBX6):c.-646G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 152,336 control chromosomes in the GnomAD database, including 13,508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.41 ( 13496 hom., cov: 33)

Exomes 𝑓: 0.35 ( 12 hom. )

Consequence

TBX6
ENST00000553607.1 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.838

Variant links:

Genes affected

TBX6 (HGNC:11605): (T-box transcription factor 6) 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. Knockout studies in mice indicate that this gene is important for specification of paraxial mesoderm structures. [provided by RefSeq, Aug 2008]

TBX6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 16-30091839-C-A is Benign according to our data. Variant chr16-30091839-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 427809.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBX6	NM_004608.4 linkuse as main transcript	c.-49+34G>T		intron_variant		ENST00000395224.7	NP_004599.2	O95947-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBX6	ENST00000553607.1 linkuse as main transcript	c.-646G>T		5_prime_UTR_variant	1/5	1		ENSP00000461223.1		O95947-2
TBX6	ENST00000395224.7 linkuse as main transcript	c.-49+34G>T		intron_variant		1	NM_004608.4	ENSP00000378650.2		O95947-1

Frequencies

GnomAD3 genomes

AF:

0.415

AC:

63030

AN:

152034

Hom.:

13469

Cov.:

show subpopulations

Gnomad AFR

AF:

0.347

Gnomad AMI

AF:

0.357

Gnomad AMR

AF:

0.481

Gnomad ASJ

AF:

0.462

Gnomad EAS

AF:

0.572

Gnomad SAS

AF:

0.485

Gnomad FIN

AF:

0.483

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.411

Gnomad OTH

AF:

0.421

GnomAD4 exome

AF:

0.348

AC:

AN:

184

Hom.:

Cov.:

AF XY:

0.358

AC XY:

AN XY:

134

show subpopulations

Gnomad4 AFR exome

AF:

0.200

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.500

Gnomad4 EAS exome

AF:

0.500

Gnomad4 SAS exome

AF:

0.328

Gnomad4 NFE exome

AF:

0.373

Gnomad4 OTH exome

AF:

0.375

GnomAD4 genome

AF:

0.415

AC:

63089

AN:

152152

Hom.:

13496

Cov.:

AF XY:

0.421

AC XY:

31330

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.347

Gnomad4 AMR

AF:

0.482

Gnomad4 ASJ

AF:

0.462

Gnomad4 EAS

AF:

0.571

Gnomad4 SAS

AF:

0.486

Gnomad4 FIN

AF:

0.483

Gnomad4 NFE

AF:

0.411

Gnomad4 OTH

AF:

0.426

Alfa

AF:

0.409

Hom.:

3413

Bravo

AF:

0.415

Asia WGS

AF:

0.582

AC:

2021

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Spondylocostal dysostosis 5

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein

Feb 18, 2021

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.5

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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