1-118884831-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001330677.2(TBX15):c.1710C>T(p.Ser570=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,614,064 control chromosomes in the GnomAD database, including 11,472 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.096 (919 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10553 hom.)
• Consequence: TBX15 NM_001330677.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.77

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 1-118884831-G-A is Benign according to our data. Variant chr1-118884831-G-A is described in ClinVar as [Benign]. Clinvar id is 1221451.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.77 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBX15	NM_001330677.2	c.1710C>T	p.Ser570=	synonymous_variant	8/8	ENST00000369429.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBX15	ENST00000369429.5	c.1710C>T	p.Ser570=	synonymous_variant	8/8	5	NM_001330677.2	P1
TBX15	ENST00000207157.7	c.1392C>T	p.Ser464=	synonymous_variant	8/8	1
TBX15	ENST00000449873.5	c.894C>T	p.Ser298=	synonymous_variant	4/4	5

Frequencies

GnomAD3 genomes AF: 0.0961 AC: 14614 AN: 152082 Hom.: 918 Cov.: 32

Gnomad AFR AF: 0.0356

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.0774

Gnomad ASJ AF: 0.0815

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.0526

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.100

GnomAD3 exomes AF: 0.104 AC: 26101 AN: 250942 Hom.: 1708 AF XY: 0.104 AC XY: 14152 AN XY: 135616

Gnomad AFR exome AF: 0.0336

Gnomad AMR exome AF: 0.0513

Gnomad ASJ exome AF: 0.0891

Gnomad EAS exome AF: 0.103

Gnomad SAS exome AF: 0.0533

Gnomad FIN exome AF: 0.210

Gnomad NFE exome AF: 0.125

Gnomad OTH exome AF: 0.103

GnomAD4 exome AF: 0.115 AC: 167450 AN: 1461864 Hom.: 10553 Cov.: 34 AF XY: 0.113 AC XY: 82385 AN XY: 727232

Gnomad4 AFR exome AF: 0.0304

Gnomad4 AMR exome AF: 0.0536

Gnomad4 ASJ exome AF: 0.0885

Gnomad4 EAS exome AF: 0.145

Gnomad4 SAS exome AF: 0.0532

Gnomad4 FIN exome AF: 0.205

Gnomad4 NFE exome AF: 0.121

Gnomad4 OTH exome AF: 0.0976

GnomAD4 genome AF: 0.0960 AC: 14612 AN: 152200 Hom.: 919 Cov.: 32 AF XY: 0.0990 AC XY: 7366 AN XY: 74380

Gnomad4 AFR AF: 0.0355

Gnomad4 AMR AF: 0.0773

Gnomad4 ASJ AF: 0.0815

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.0522

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.0997

Alfa AF: 0.104 Hom.: 712

Bravo AF: 0.0856

Asia WGS AF: 0.0650 AC: 227 AN: 3478

EpiCase AF: 0.110

EpiControl AF: 0.115

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 02, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Pelviscapular dysplasia Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	6.2
Dann	Benign	0.58

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: rs12569041; hg19: chr1-119427454; COSMIC: COSV52868815;