1-118884605-GAAAAAAAAAA-GAAA

Variant names:

• chr1-118884605-GAAAAAAA-G
• rs536044359
• NM_001330677.2:c.*120_*126delTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001330677.2(TBX15):​c.*120_*126delTTTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 689,228 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: TBX15 NM_001330677.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX15	NM_001330677.2	c.*120_*126delTTTTTTT		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.*120_*126delTTTTTTT		3_prime_UTR_variant	Exon 8 of 8	5	NM_001330677.2	ENSP00000358437.3
TBX15	ENST00000207157.7	c.*120_*126delTTTTTTT		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000207157.3
TBX15	ENST00000449873.5	c.*120_*126delTTTTTTT		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000398625.1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 0.0000116 AC: 8 AN: 689228 Hom.: 0 AF XY: 0.0000142 AC XY: 5 AN XY: 352772

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

African (AFR) AF: 0.00 AC: 0 AN: 16366

American (AMR) AF: 0.00 AC: 0 AN: 18866

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14718

East Asian (EAS) AF: 0.00 AC: 0 AN: 29742

South Asian (SAS) AF: 0.00 AC: 0 AN: 48914

European-Finnish (FIN) AF: 0.0000347 AC: 1 AN: 28858

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2334

European-Non Finnish (NFE) AF: 0.0000121 AC: 6 AN: 496628

Other (OTH) AF: 0.0000305 AC: 1 AN: 32802

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000112799), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs536044359; hg19: chr1-119427228;