rs10494217

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001330677.2(TBX15):c.466C>A(p.His156Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,612,184 control chromosomes in the GnomAD database, including 23,715 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1784 hom., cov: 33)

Exomes 𝑓: 0.17 ( 21931 hom. )

Consequence

TBX15
NM_001330677.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 10.0

Publications

47 publications found

Variant links:

Genes affected

TBX15 (HGNC:11594): (T-box transcription factor 15) This gene belongs to the T-box family of genes, which encode a phylogenetically conserved family of transcription factors that regulate a variety of developmental processes. All these genes contain a common T-box DNA-binding domain. Mutations in this gene are associated with Cousin syndrome.[provided by RefSeq, Oct 2009]

TBX15 Gene-Disease associations (from GenCC):

pelviscapular dysplasia
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet

TBX15 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017850101).

BP6

Variant 1-118926565-G-T is Benign according to our data. Variant chr1-118926565-G-T is described in ClinVar as Benign. ClinVar VariationId is 1240908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX15	NM_001330677.2 link	c.466C>A	p.His156Asn	missense_variant	Exon 3 of 8	ENST00000369429.5	NP_001317606.1	Q96SF7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBX15	ENST00000369429.5 link	c.466C>A	p.His156Asn	missense_variant	Exon 3 of 8	5	NM_001330677.2	ENSP00000358437.3		Q96SF7-1
TBX15	ENST00000207157.7 link	c.148C>A	p.His50Asn	missense_variant	Exon 3 of 8	1		ENSP00000207157.3		Q96SF7-2

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19557

AN:

152108

Hom.:

1782

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0289

Gnomad AMI

AF:

0.132

Gnomad AMR

AF:

0.104

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.0704

Gnomad SAS

AF:

0.0978

Gnomad FIN

AF:

0.280

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.179

Gnomad OTH

AF:

0.122

GnomAD2 exomes

AF:

0.144

AC:

36201

AN:

250946

AF XY:

0.146

show subpopulations

Gnomad AFR exome

AF:

0.0247

Gnomad AMR exome

AF:

0.0855

Gnomad ASJ exome

AF:

0.123

Gnomad EAS exome

AF:

0.0729

Gnomad FIN exome

AF:

0.282

Gnomad NFE exome

AF:

0.180

Gnomad OTH exome

AF:

0.148

GnomAD4 exome

AF:

0.166

AC:

241900

AN:

1459958

Hom.:

21931

Cov.:

AF XY:

0.164

AC XY:

119119

AN XY:

726340

show subpopulations

African (AFR)

AF:

0.0234

AC:

782

AN:

33468

American (AMR)

AF:

0.0865

AC:

3866

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.118

AC:

3083

AN:

26122

East Asian (EAS)

AF:

0.0623

AC:

2473

AN:

39670

South Asian (SAS)

AF:

0.0951

AC:

8201

AN:

86220

European-Finnish (FIN)

AF:

0.276

AC:

14739

AN:

53366

Middle Eastern (MID)

AF:

0.0760

AC:

438

AN:

5762

European-Non Finnish (NFE)

AF:

0.180

AC:

199364

AN:

1110334

Other (OTH)

AF:

0.148

AC:

8954

AN:

60308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

9623

19246

28869

38492

48115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6750

13500

20250

27000

33750

<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:

0.128

AC:

19558

AN:

152226

Hom.:

1784

Cov.:

AF XY:

0.132

AC XY:

9828

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0288

AC:

1197

AN:

41544

American (AMR)

AF:

0.104

AC:

1596

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.114

AC:

396

AN:

3470

East Asian (EAS)

AF:

0.0709

AC:

368

AN:

5190

South Asian (SAS)

AF:

0.0977

AC:

472

AN:

4830

European-Finnish (FIN)

AF:

0.280

AC:

2957

AN:

10572

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.179

AC:

12174

AN:

67998

Other (OTH)

AF:

0.121

AC:

257

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

835

1670

2506

3341

4176

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

216

432

648

864

1080

<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:

0.154

Hom.:

7092

Bravo

AF:

0.112

TwinsUK

AF:

0.172

AC:

638

ALSPAC

AF:

0.175

AC:

675

ESP6500AA

AF:

0.0343

AC:

151

ESP6500EA

AF:

0.181

AC:

1560

ExAC

AF:

0.144

AC:

17519

Asia WGS

AF:

0.100

AC:

346

AN:

3478

EpiCase

AF:

0.161

EpiControl

AF:

0.165

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

- -

Pelviscapular dysplasia

Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.26

.;T

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.85

T;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-0.38

MutationAssessor

Benign

0.35

.;N

PhyloP100

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-2.0

N;N

REVEL

Uncertain

0.35

Sift

Benign

0.47

T;T

Sift4G

Benign

0.50

T;T

Polyphen

0.12

.;B

Vest4

0.31

MPC

0.35

ClinPred

0.054

GERP RS

6.1

Varity_R

0.29

gMVP

0.20

Mutation Taster

=19/81

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