Variant 16-30086309-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004608.4(TBX6):c.1227G>A(p.Pro409=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 1,610,118 control chromosomes in the GnomAD database, including 90,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P409P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.27 ( 6811 hom., cov: 32)

Exomes 𝑓: 0.33 ( 83970 hom. )

Consequence

TBX6
NM_004608.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.57

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 16-30086309-C-T is Benign according to our data. Variant chr16-30086309-C-T is described in ClinVar as [Benign]. Clinvar id is 259448.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.57 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TBX6	NM_004608.4 linkuse as main transcript	c.1227G>A	p.Pro409=	synonymous_variant	9/9	ENST00000395224.7
TBX6	XM_011545926.4 linkuse as main transcript	c.1227G>A	p.Pro409=	synonymous_variant	9/9
TBX6	XM_047434551.1 linkuse as main transcript	c.1227G>A	p.Pro409=	synonymous_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBX6	ENST00000395224.7 linkuse as main transcript	c.1227G>A	p.Pro409=	synonymous_variant	9/9	1	NM_004608.4	P1	O95947-1
TBX6	ENST00000279386.6 linkuse as main transcript	c.1227G>A	p.Pro409=	synonymous_variant	8/8	1		P1	O95947-1
TBX6	ENST00000567664.5 linkuse as main transcript	c.*361G>A		3_prime_UTR_variant, NMD_transcript_variant	7/7	5			O95947-2

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40659

AN:

151964

Hom.:

6809

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0695

Gnomad AMI

AF:

0.361

Gnomad AMR

AF:

0.298

Gnomad ASJ

AF:

0.317

Gnomad EAS

AF:

0.469

Gnomad SAS

AF:

0.233

Gnomad FIN

AF:

0.420

Gnomad MID

AF:

0.299

Gnomad NFE

AF:

0.341

Gnomad OTH

AF:

0.283

GnomAD3 exomes

AF:

0.326

AC:

79650

AN:

244618

Hom.:

13959

AF XY:

0.324

AC XY:

43120

AN XY:

133162

show subpopulations

Gnomad AFR exome

AF:

0.0610

Gnomad AMR exome

AF:

0.340

Gnomad ASJ exome

AF:

0.312

Gnomad EAS exome

AF:

0.456

Gnomad SAS exome

AF:

0.231

Gnomad FIN exome

AF:

0.417

Gnomad NFE exome

AF:

0.347

Gnomad OTH exome

AF:

0.340

GnomAD4 exome

AF:

0.333

AC:

485194

AN:

1458036

Hom.:

83970

Cov.:

AF XY:

0.330

AC XY:

239636

AN XY:

725400

show subpopulations

Gnomad4 AFR exome

AF:

0.0592

Gnomad4 AMR exome

AF:

0.340

Gnomad4 ASJ exome

AF:

0.307

Gnomad4 EAS exome

AF:

0.535

Gnomad4 SAS exome

AF:

0.231

Gnomad4 FIN exome

AF:

0.426

Gnomad4 NFE exome

AF:

0.339

Gnomad4 OTH exome

AF:

0.317

GnomAD4 genome

AF:

0.267

AC:

40667

AN:

152082

Hom.:

6811

Cov.:

AF XY:

0.271

AC XY:

20158

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.0694

Gnomad4 AMR

AF:

0.298

Gnomad4 ASJ

AF:

0.317

Gnomad4 EAS

AF:

0.468

Gnomad4 SAS

AF:

0.233

Gnomad4 FIN

AF:

0.420

Gnomad4 NFE

AF:

0.341

Gnomad4 OTH

AF:

0.286

Alfa

AF:

0.282

Hom.:

3062

Bravo

AF:

0.257

Asia WGS

AF:

0.354

AC:

1229

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 28, 2016	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 04, 2022	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.45

DANN

Benign

0.89

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