chr1-118884605-G-GA

Variant names:

• chr1-118884605-G-GA
• rs536044359
• NM_001330677.2:c.*126dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001330677.2(TBX15):​c.*126dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 749,066 control chromosomes in the GnomAD database, including 490 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (468 hom., cov: 27)
  • Exomes 𝑓: 0.28 (22 hom.)
• Consequence: TBX15 NM_001330677.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.512
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 1-118884605-G-GA is Benign according to our data. Variant chr1-118884605-G-GA is described in ClinVar as Benign. ClinVar VariationId is 1297885.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX15	NM_001330677.2	c.*126dupT		3_prime_UTR_variant	Exon 8 of 8	ENST00000369429.5	NP_001317606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBX15	ENST00000369429.5	c.*126dupT		3_prime_UTR_variant	Exon 8 of 8	5	NM_001330677.2	ENSP00000358437.3
TBX15	ENST00000207157.7	c.*126dupT		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000207157.3
TBX15	ENST00000449873.5	c.*126dupT		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000398625.1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 8867 AN: 80604 Hom.: 469 Cov.: 27

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.0764

Gnomad AMR AF: 0.0981

Gnomad ASJ AF: 0.0820

Gnomad EAS AF: 0.0268

Gnomad SAS AF: 0.0544

Gnomad FIN AF: 0.0438

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.0749

Gnomad OTH AF: 0.117

GnomAD4 exome AF: 0.280 AC: 187466 AN: 668442 Hom.: 22 Cov.: 6 AF XY: 0.281 AC XY: 95928 AN XY: 341640

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

African (AFR) AF: 0.233 AC: 3683 AN: 15782

American (AMR) AF: 0.289 AC: 5188 AN: 17980

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 3961 AN: 14140

East Asian (EAS) AF: 0.291 AC: 8246 AN: 28376

South Asian (SAS) AF: 0.288 AC: 13357 AN: 46454

European-Finnish (FIN) AF: 0.262 AC: 7275 AN: 27812

Middle Eastern (MID) AF: 0.293 AC: 660 AN: 2256

European-Non Finnish (NFE) AF: 0.281 AC: 136168 AN: 483956

Other (OTH) AF: 0.282 AC: 8928 AN: 31686

⚠️ 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.

GnomAD4 genome AF: 0.110 AC: 8864 AN: 80624 Hom.: 468 Cov.: 27 AF XY: 0.110 AC XY: 4169 AN XY: 37788

African (AFR) AF: 0.179 AC: 4870 AN: 27180

American (AMR) AF: 0.0979 AC: 666 AN: 6806

Ashkenazi Jewish (ASJ) AF: 0.0820 AC: 158 AN: 1926

East Asian (EAS) AF: 0.0268 AC: 58 AN: 2168

South Asian (SAS) AF: 0.0532 AC: 107 AN: 2010

European-Finnish (FIN) AF: 0.0438 AC: 139 AN: 3172

Middle Eastern (MID) AF: 0.263 AC: 30 AN: 114

European-Non Finnish (NFE) AF: 0.0749 AC: 2677 AN: 35754

Other (OTH) AF: 0.118 AC: 128 AN: 1088

Alfa AF: 0.00551 Hom.: 6

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 15, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs536044359; hg19: chr1-119427228; COSMIC: COSV52876750;