1-118884605-G-GAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001330677.2(TBX15):c.*126_*127insTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0659 in 734,556 control chromosomes in the GnomAD database, including 50 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.034 (45 hom., cov: 27)
  • Exomes 𝑓: 0.070 (5 hom.)
• Consequence: TBX15 NM_001330677.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.512

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-G-GAA is Benign according to our data. Variant chr1-118884605-G-GAA is described in ClinVar as [Benign]. Clinvar id is 1253783.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.074 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBX15	NM_001330677.2	c.*126_*127insTT		3_prime_UTR_variant	8/8	ENST00000369429.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBX15	ENST00000369429.5	c.*126_*127insTT		3_prime_UTR_variant	8/8	5	NM_001330677.2	P1
TBX15	ENST00000207157.7	c.*126_*127insTT		3_prime_UTR_variant	8/8	1
TBX15	ENST00000449873.5	c.*126_*127insTT		3_prime_UTR_variant	4/4	5

Frequencies

GnomAD3 genomes AF: 0.0339 AC: 2734 AN: 80692 Hom.: 45 Cov.: 27

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.0172

Gnomad AMR AF: 0.0280

Gnomad ASJ AF: 0.0140

Gnomad EAS AF: 0.000921

Gnomad SAS AF: 0.0110

Gnomad FIN AF: 0.0924

Gnomad MID AF: 0.0250

Gnomad NFE AF: 0.0500

Gnomad OTH AF: 0.0265

GnomAD4 exome AF: 0.0699 AC: 45685 AN: 653844 Hom.: 5 Cov.: 6 AF XY: 0.0701 AC XY: 23407 AN XY: 334040

Gnomad4 AFR exome AF: 0.0678

Gnomad4 AMR exome AF: 0.0669

Gnomad4 ASJ exome AF: 0.0650

Gnomad4 EAS exome AF: 0.0505

Gnomad4 SAS exome AF: 0.0761

Gnomad4 FIN exome AF: 0.0725

Gnomad4 NFE exome AF: 0.0707

Gnomad4 OTH exome AF: 0.0685

GnomAD4 genome AF: 0.0339 AC: 2736 AN: 80712 Hom.: 45 Cov.: 27 AF XY: 0.0346 AC XY: 1310 AN XY: 37838

Gnomad4 AFR AF: 0.0137

Gnomad4 AMR AF: 0.0280

Gnomad4 ASJ AF: 0.0140

Gnomad4 EAS AF: 0.000921

Gnomad4 SAS AF: 0.0114

Gnomad4 FIN AF: 0.0924

Gnomad4 NFE AF: 0.0500

Gnomad4 OTH AF: 0.0266

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 18, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

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;