chr16-30088717-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_004608.4(TBX6):c.744C>T(p.Ser248Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,614,140 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 5 hom. )

Consequence

TBX6
NM_004608.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -8.99

Publications

0 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):

Mayer-Rokitansky-Kuster-Hauser syndrome
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
spondylocostal dysostosis 5
Inheritance: Unknown, AR, SD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, 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=-0.77).

BP6

Variant 16-30088717-G-A is Benign according to our data. Variant chr16-30088717-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 259449.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-8.99 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00126 (192/152278) while in subpopulation SAS AF = 0.00374 (18/4818). AF 95% confidence interval is 0.00241. There are 0 homozygotes in GnomAd4. There are 118 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 5 AR,Unknown,AD,SD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004608.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX6	NM_004608.4	MANE Select	c.744C>T	p.Ser248Ser	synonymous	Exon 5 of 9	NP_004599.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBX6	ENST00000395224.7	TSL:1 MANE Select	c.744C>T	p.Ser248Ser	synonymous	Exon 5 of 9	ENSP00000378650.2	O95947-1
TBX6	ENST00000279386.6	TSL:1	c.744C>T	p.Ser248Ser	synonymous	Exon 4 of 8	ENSP00000279386.2	O95947-1
TBX6	ENST00000553607.1	TSL:1	c.744C>T	p.Ser248Ser	synonymous	Exon 4 of 5	ENSP00000461223.1	O95947-2

Frequencies

GnomAD3 genomes

AF:

0.00126

AC:

192

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.00602

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00143

Gnomad OTH

AF:

0.000958

GnomAD2 exomes

AF:

0.00173

AC:

434

AN:

251408

AF XY:

0.00208

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00444

Gnomad NFE exome

AF:

0.00148

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00144

AC:

2112

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00163

AC XY:

1189

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33478

American (AMR)

AF:

0.000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00576

AC:

497

AN:

86258

European-Finnish (FIN)

AF:

0.00369

AC:

197

AN:

53414

Middle Eastern (MID)

AF:

0.00277

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00118

AC:

1308

AN:

1111988

Other (OTH)

AF:

0.00136

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

160

319

479

638

798

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

126

168

210

<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:

0.00126

AC:

192

AN:

152278

Hom.:

Cov.:

AF XY:

0.00158

AC XY:

118

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.000168

AC:

AN:

41560

American (AMR)

AF:

0.000131

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00374

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00602

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00143

AC:

AN:

68022

Other (OTH)

AF:

0.000948

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00137

Hom.:

Bravo

AF:

0.000638

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00153

EpiControl

AF:

0.00130

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.42

(source)

DANN

Benign

0.80

PhyloP100

-9.0

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over