1-118884605-GAAAA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001330677.2(TBX15):c.*123_*126del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00251 in 767,070 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0082 (5 hom., cov: 27)
  • Exomes 𝑓: 0.0018 (0 hom.)
• Consequence: TBX15 NM_001330677.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.818

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-118884605-GAAAA-G is Benign according to our data. Variant chr1-118884605-GAAAA-G is described in ClinVar as [Likely_benign]. Clinvar id is 1214267.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00818 (661/80766) while in subpopulation AFR AF= 0.023 (625/27214). AF 95% confidence interval is 0.0215. There are 5 homozygotes in gnomad4. There are 310 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBX15	NM_001330677.2	c.*123_*126del		3_prime_UTR_variant	8/8	ENST00000369429.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBX15	ENST00000369429.5	c.*123_*126del		3_prime_UTR_variant	8/8	5	NM_001330677.2	P1
TBX15	ENST00000207157.7	c.*123_*126del		3_prime_UTR_variant	8/8	1
TBX15	ENST00000449873.5	c.*123_*126del		3_prime_UTR_variant	4/4	5

Frequencies

GnomAD3 genomes AF: 0.00820 AC: 662 AN: 80746 Hom.: 5 Cov.: 27

Gnomad AFR AF: 0.0230

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.00155

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000167

Gnomad OTH AF: 0.00548

GnomAD4 exome AF: 0.00184 AC: 1262 AN: 686304 Hom.: 0 AF XY: 0.00169 AC XY: 592 AN XY: 351298

Gnomad4 AFR exome AF: 0.0179

Gnomad4 AMR exome AF: 0.00197

Gnomad4 ASJ exome AF: 0.00253

Gnomad4 EAS exome AF: 0.00129

Gnomad4 SAS exome AF: 0.000718

Gnomad4 FIN exome AF: 0.00129

Gnomad4 NFE exome AF: 0.00143

Gnomad4 OTH exome AF: 0.00236

GnomAD4 genome AF: 0.00818 AC: 661 AN: 80766 Hom.: 5 Cov.: 27 AF XY: 0.00819 AC XY: 310 AN XY: 37852

Gnomad4 AFR AF: 0.0230

Gnomad4 AMR AF: 0.00308

Gnomad4 ASJ AF: 0.00155

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000167

Gnomad4 OTH AF: 0.00549

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 19, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs536044359; hg19: chr1-119427228;