Variant 1-118884844-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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. Variant chr1-118884844-A-C is described in Lovd as [Likely_benign].

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/exons	MANE	Protein	UniProt
TBX15	NM_001330677.2 linkuse as main transcript	c.1697T>G	p.Met566Arg	missense_variant	8/8	ENST00000369429.5	NP_001317606.1	Q96SF7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TBX15	ENST00000369429.5 linkuse as main transcript	c.1697T>G	p.Met566Arg	missense_variant	8/8	5	NM_001330677.2	ENSP00000358437.3	Q96SF7-1
TBX15	ENST00000207157.7 linkuse as main transcript	c.1379T>G	p.Met460Arg	missense_variant	8/8	1		ENSP00000207157.3	Q96SF7-2
TBX15	ENST00000449873.5 linkuse as main transcript	c.881T>G	p.Met294Arg	missense_variant	4/4	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

GnomAD3 exomes

AF:

0.0446

AC:

11198

AN:

250914

Hom.:

392

AF XY:

0.0497

AC XY:

6737

AN XY:

135586

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 SAS exome

AF:

0.0986

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

Gnomad4 AFR exome

AF:

0.00630

Gnomad4 AMR exome

AF:

0.0332

Gnomad4 ASJ exome

AF:

0.0936

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.0996

Gnomad4 FIN exome

AF:

0.0201

Gnomad4 NFE exome

AF:

0.0462

Gnomad4 OTH exome

AF:

0.0484

GnomAD4 genome

AF:

0.0341

AC:

5198

AN:

152298

Hom.:

153

Cov.:

AF XY:

0.0343

AC XY:

2555

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00811

Gnomad4 AMR

AF:

0.0411

Gnomad4 ASJ

AF:

0.104

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.0967

Gnomad4 FIN

AF:

0.0195

Gnomad4 NFE

AF:

0.0449

Gnomad4 OTH

AF:

0.0473

Alfa

AF:

0.0438

Hom.:

256

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 16, 2019	This variant is associated with the following publications: (PMID: 28146470) -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Oct 20, 2017

- -

Pelviscapular dysplasia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

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

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

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

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