dbSNP rs10494217: TBX15:p.His156Asn (chr1-118926565-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -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 (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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=0.0017850101).

BP6

Variant 1-118926565-G-T is Benign according to our data. Variant chr1-118926565-G-T is described in ClinVar as [Benign]. Clinvar id 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

GnomAD3 exomes

AF:

0.144

AC:

36201

AN:

250946

Hom.:

3229

AF XY:

0.146

AC XY:

19743

AN XY:

135630

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 SAS exome

AF:

0.0944

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

Gnomad4 AFR exome

AF:

0.0234

Gnomad4 AMR exome

AF:

0.0865

Gnomad4 ASJ exome

AF:

0.118

Gnomad4 EAS exome

AF:

0.0623

Gnomad4 SAS exome

AF:

0.0951

Gnomad4 FIN exome

AF:

0.276

Gnomad4 NFE exome

AF:

0.180

Gnomad4 OTH exome

AF:

0.148

GnomAD4 genome

AF:

0.128

AC:

19558

AN:

152226

Hom.:

1784

Cov.:

AF XY:

0.132

AC XY:

9828

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0288

Gnomad4 AMR

AF:

0.104

Gnomad4 ASJ

AF:

0.114

Gnomad4 EAS

AF:

0.0709

Gnomad4 SAS

AF:

0.0977

Gnomad4 FIN

AF:

0.280

Gnomad4 NFE

AF:

0.179

Gnomad4 OTH

AF:

0.121

Alfa

AF:

0.163

Hom.:

5315

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

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

- -

Nov 12, 2018

GeneDx

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

Benign

0.22

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

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

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

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