chr16-30086309-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004608.4(TBX6):c.1227G>A(p.Pro409Pro) 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:6

Conservation

PhyloP100: -2.57

Publications

51 publications found

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 Gene-Disease associations (from GenCC):

spondylocostal dysostosis 5
Inheritance: Unknown, SD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
autosomal dominant spondylocostal dysostosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
congenital anomaly of kidney and urinary tract
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

TBX6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
TBX6	NM_004608.4 link	c.1227G>A	p.Pro409Pro	synonymous_variant	Exon 9 of 9	ENST00000395224.7	NP_004599.2	O95947-1
TBX6	XM_011545926.4 link	c.1227G>A	p.Pro409Pro	synonymous_variant	Exon 9 of 9		XP_011544228.1	O95947-1
TBX6	XM_047434551.1 link	c.1227G>A	p.Pro409Pro	synonymous_variant	Exon 8 of 8		XP_047290507.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TBX6	ENST00000395224.7 link	c.1227G>A	p.Pro409Pro	synonymous_variant	Exon 9 of 9	1	NM_004608.4	ENSP00000378650.2	O95947-1
TBX6	ENST00000279386.6 link	c.1227G>A	p.Pro409Pro	synonymous_variant	Exon 8 of 8	1		ENSP00000279386.2	O95947-1
TBX6	ENST00000567664.5 link	n.*361G>A		non_coding_transcript_exon_variant	Exon 7 of 7	5		ENSP00000460425.1	O95947-2
TBX6	ENST00000567664.5 link	n.*361G>A		3_prime_UTR_variant	Exon 7 of 7	5		ENSP00000460425.1	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

GnomAD2 exomes

AF:

0.326

AC:

79650

AN:

244618

AF XY:

0.324

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 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

African (AFR)

AF:

0.0592

AC:

1973

AN:

33328

American (AMR)

AF:

0.340

AC:

14906

AN:

43838

Ashkenazi Jewish (ASJ)

AF:

0.307

AC:

7959

AN:

25938

East Asian (EAS)

AF:

0.535

AC:

21178

AN:

39612

South Asian (SAS)

AF:

0.231

AC:

19913

AN:

86070

European-Finnish (FIN)

AF:

0.426

AC:

22698

AN:

53308

Middle Eastern (MID)

AF:

0.266

AC:

1310

AN:

4918

European-Non Finnish (NFE)

AF:

0.339

AC:

376207

AN:

1110896

Other (OTH)

AF:

0.317

AC:

19050

AN:

60128

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

20085

40170

60255

80340

100425

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11980

23960

35940

47920

59900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.267

AC:

40667

AN:

152082

Hom.:

6811

Cov.:

AF XY:

0.271

AC XY:

20158

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.0694

AC:

2883

AN:

41524

American (AMR)

AF:

0.298

AC:

4557

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.317

AC:

1100

AN:

3472

East Asian (EAS)

AF:

0.468

AC:

2412

AN:

5150

South Asian (SAS)

AF:

0.233

AC:

1123

AN:

4824

European-Finnish (FIN)

AF:

0.420

AC:

4440

AN:

10582

Middle Eastern (MID)

AF:

0.298

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.341

AC:

23131

AN:

67930

Other (OTH)

AF:

0.286

AC:

605

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1402

2804

4205

5607

7009

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

410

820

1230

1640

2050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Mar 28, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 04, 2022

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.45

(source)

DANN

Benign

0.89

PhyloP100

-2.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over