1-118884831-G-A

Variant names:

• chr1-118884831-G-A
• rs12569041
• NM_001330677.2:c.1710C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001330677.2(TBX15):​c.1710C>T​(p.Ser570Ser) 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:4
• Conservation: PhyloP100: 1.77
• Publications: 20 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 -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 rank	MANE	Protein	UniProt
TBX15	NM_001330677.2	c.1710C>T	p.Ser570Ser	synonymous_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.1710C>T	p.Ser570Ser	synonymous_variant	Exon 8 of 8	5	NM_001330677.2	ENSP00000358437.3
TBX15	ENST00000207157.7	c.1392C>T	p.Ser464Ser	synonymous_variant	Exon 8 of 8	1		ENSP00000207157.3
TBX15	ENST00000449873.5	c.894C>T	p.Ser298Ser	synonymous_variant	Exon 4 of 4	5		ENSP00000398625.1

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

GnomAD2 exomes AF: 0.104 AC: 26101 AN: 250942 AF XY: 0.104

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 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

African (AFR) AF: 0.0304 AC: 1019 AN: 33480

American (AMR) AF: 0.0536 AC: 2398 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0885 AC: 2312 AN: 26134

East Asian (EAS) AF: 0.145 AC: 5767 AN: 39698

South Asian (SAS) AF: 0.0532 AC: 4592 AN: 86256

European-Finnish (FIN) AF: 0.205 AC: 10929 AN: 53418

Middle Eastern (MID) AF: 0.0541 AC: 312 AN: 5766

European-Non Finnish (NFE) AF: 0.121 AC: 134225 AN: 1111996

Other (OTH) AF: 0.0976 AC: 5896 AN: 60394

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

African (AFR) AF: 0.0355 AC: 1477 AN: 41558

American (AMR) AF: 0.0773 AC: 1182 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0815 AC: 283 AN: 3472

East Asian (EAS) AF: 0.111 AC: 572 AN: 5158

South Asian (SAS) AF: 0.0522 AC: 252 AN: 4826

European-Finnish (FIN) AF: 0.213 AC: 2256 AN: 10570

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8228 AN: 68000

Other (OTH) AF: 0.0997 AC: 211 AN: 2116

Alfa AF: 0.104 Hom.: 779

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 02, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Pelviscapular dysplasia Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.2
DANN	Benign	0.58
PhyloP100		1.8
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: rs12569041; hg19: chr1-119427454; COSMIC: COSV52868815;