rs61730011

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1697T>G(p.Met566Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0456 in 1,614,162 control chromosomes in the GnomAD database, including 2,170 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 153 hom., cov: 32)

Exomes 𝑓: 0.047 ( 2017 hom. )

Consequence

TBX15
NM_001330677.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 8.60

Publications

18 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=0.0022727847).

BP6

Variant 1-118884844-A-C is Benign according to our data. Variant chr1-118884844-A-C is described in ClinVar as [Benign]. Clinvar id is 594474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX15	NM_001330677.2 link	c.1697T>G	p.Met566Arg	missense_variant	Exon 8 of 8	ENST00000369429.5	NP_001317606.1	Q96SF7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TBX15	ENST00000369429.5 link	c.1697T>G	p.Met566Arg	missense_variant	Exon 8 of 8	5	NM_001330677.2	ENSP00000358437.3	Q96SF7-1
TBX15	ENST00000207157.7 link	c.1379T>G	p.Met460Arg	missense_variant	Exon 8 of 8	1		ENSP00000207157.3	Q96SF7-2
TBX15	ENST00000449873.5 link	c.881T>G	p.Met294Arg	missense_variant	Exon 4 of 4	5		ENSP00000398625.1	Q5JT55

Frequencies

GnomAD3 genomes

AF:

0.0342

AC:

5202

AN:

152180

Hom.:

154

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00813

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0412

Gnomad ASJ

AF:

0.104

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0975

Gnomad FIN

AF:

0.0195

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0448

Gnomad OTH

AF:

0.0478

GnomAD2 exomes

AF:

0.0446

AC:

11198

AN:

250914

AF XY:

0.0497

show subpopulations

Gnomad AFR exome

AF:

0.00560

Gnomad AMR exome

AF:

0.0321

Gnomad ASJ exome

AF:

0.0955

Gnomad EAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.0202

Gnomad NFE exome

AF:

0.0464

Gnomad OTH exome

AF:

0.0521

GnomAD4 exome

AF:

0.0468

AC:

68487

AN:

1461864

Hom.:

2017

Cov.:

AF XY:

0.0489

AC XY:

35596

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.00630

AC:

211

AN:

33480

American (AMR)

AF:

0.0332

AC:

1483

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0936

AC:

2447

AN:

26136

East Asian (EAS)

AF:

0.000227

AC:

AN:

39694

South Asian (SAS)

AF:

0.0996

AC:

8589

AN:

86258

European-Finnish (FIN)

AF:

0.0201

AC:

1072

AN:

53420

Middle Eastern (MID)

AF:

0.0734

AC:

423

AN:

5766

European-Non Finnish (NFE)

AF:

0.0462

AC:

51331

AN:

1111992

Other (OTH)

AF:

0.0484

AC:

2922

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

4460

8920

13379

17839

22299

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0341

AC:

5198

AN:

152298

Hom.:

153

Cov.:

AF XY:

0.0343

AC XY:

2555

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.00811

AC:

337

AN:

41572

American (AMR)

AF:

0.0411

AC:

629

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.104

AC:

360

AN:

3470

East Asian (EAS)

AF:

0.000965

AC:

AN:

5184

South Asian (SAS)

AF:

0.0967

AC:

466

AN:

4818

European-Finnish (FIN)

AF:

0.0195

AC:

207

AN:

10614

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0449

AC:

3053

AN:

68026

Other (OTH)

AF:

0.0473

AC:

100

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

251

503

754

1006

1257

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0424

Hom.:

593

Bravo

AF:

0.0333

TwinsUK

AF:

0.0402

AC:

149

ALSPAC

AF:

0.0516

AC:

199

ESP6500AA

AF:

0.00635

AC:

ESP6500EA

AF:

0.0478

AC:

411

ExAC

AF:

0.0441

AC:

5355

Asia WGS

AF:

0.0330

AC:

114

AN:

3478

EpiCase

AF:

0.0545

EpiControl

AF:

0.0543

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 16, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 28146470) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Oct 20, 2017

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Uncertain

0.56

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.071

.;T;T

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.84

T;T;T

MetaRNN

Benign

0.0023

T;T;T

MetaSVM

Uncertain

0.10

MutationAssessor

Benign

2.0

.;.;M

PhyloP100

8.6

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.9

N;D;N

REVEL

Uncertain

0.39

Sift

Uncertain

0.0030

D;D;D

Sift4G

Uncertain

0.019

D;T;D

Polyphen

0.98

.;.;D

Vest4

0.41

MPC

0.52

ClinPred

0.049

GERP RS

5.3

Varity_R

0.79

gMVP

0.74

Mutation Taster

=52/48

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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rs61730011

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