Genetic Variant NM_001330677.2:c.*125_*126delTT (chr1-118884605-GAA-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_001330677.2(TBX15):c.*125_*126delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0156 in 759,136 control chromosomes in the GnomAD database, including 23 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.017 ( 23 hom., cov: 27)

Exomes 𝑓: 0.015 ( 0 hom. )

Consequence

TBX15
NM_001330677.2 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.818

Publications

0 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 -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0167 (1348/80768) while in subpopulation AFR AF = 0.0469 (1276/27214). AF 95% confidence interval is 0.0447. There are 23 homozygotes in GnomAd4. There are 647 alleles in the male GnomAd4 subpopulation. Median coverage is 27. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX15	NM_001330677.2 link	c.125_126delTT		3_prime_UTR_variant	Exon 8 of 8	ENST00000369429.5	NP_001317606.1	Q96SF7-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TBX15	ENST00000369429.5 link	c.125_126delTT	3_prime_UTR_variant	Exon 8 of 8	5	NM_001330677.2	ENSP00000358437.3	Q96SF7-1
TBX15	ENST00000207157.7 link	c.125_126delTT	3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000207157.3	Q96SF7-2
TBX15	ENST00000449873.5 link	c.125_126delTT	3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000398625.1	Q5JT55

Frequencies

GnomAD3 genomes

AF:

0.0167

AC:

1347

AN:

80748

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0469

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00734

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000461

Gnomad SAS

AF:

0.000997

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000251

Gnomad OTH

AF:

0.00914

GnomAD4 exome

AF:

0.0155

AC:

10482

AN:

678368

Hom.:

AF XY:

0.0153

AC XY:

5303

AN XY:

347194

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0466

AC:

746

AN:

16020

American (AMR)

AF:

0.0163

AC:

303

AN:

18558

Ashkenazi Jewish (ASJ)

AF:

0.0186

AC:

268

AN:

14444

East Asian (EAS)

AF:

0.0181

AC:

527

AN:

29092

South Asian (SAS)

AF:

0.00993

AC:

478

AN:

48152

European-Finnish (FIN)

AF:

0.0151

AC:

427

AN:

28322

Middle Eastern (MID)

AF:

0.0175

AC:

AN:

2292

European-Non Finnish (NFE)

AF:

0.0145

AC:

7088

AN:

489266

Other (OTH)

AF:

0.0188

AC:

605

AN:

32222

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.271

Heterozygous variant carriers

1003

2006

3008

4011

5014

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

202

404

606

808

1010

<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:

0.0167

AC:

1348

AN:

80768

Hom.:

Cov.:

AF XY:

0.0171

AC XY:

647

AN XY:

37856

show subpopulations

African (AFR)

AF:

0.0469

AC:

1276

AN:

27214

American (AMR)

AF:

0.00733

AC:

AN:

6822

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1932

East Asian (EAS)

AF:

0.000461

AC:

AN:

2170

South Asian (SAS)

AF:

0.000993

AC:

AN:

2014

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3176

Middle Eastern (MID)

AF:

0.00

AC:

AN:

114

European-Non Finnish (NFE)

AF:

0.000251

AC:

AN:

35826

Other (OTH)

AF:

0.00916

AC:

AN:

1092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

114

171

228

285

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.82

Mutation Taster

=100/0

polymorphism

(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

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

NM_001330677.2:c.125_126delTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over