1-118884746-C-A

Variant names:

• chr1-118884746-C-A
• rs922050997
• NM_001330677.2:c.1795G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001330677.2(TBX15):​c.1795G>T​(p.Val599Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V599M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TBX15 NM_001330677.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.49
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28645074).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX15	NM_001330677.2	c.1795G>T	p.Val599Leu	missense_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.1795G>T	p.Val599Leu	missense_variant	Exon 8 of 8	5	NM_001330677.2	ENSP00000358437.3
TBX15	ENST00000207157.7	c.1477G>T	p.Val493Leu	missense_variant	Exon 8 of 8	1		ENSP00000207157.3
TBX15	ENST00000449873.5	c.979G>T	p.Val327Leu	missense_variant	Exon 4 of 4	5		ENSP00000398625.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	.;T;T
Eigen	Benign	0.10
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Uncertain	0.0011	D
MutationAssessor	Benign	1.8	.;.;L
PhyloP100		4.5
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.29	N;N;N
REVEL	Benign	0.27
Sift	Benign	0.058	T;T;T
Sift4G	Benign	0.28	T;T;T
Polyphen		0.19	.;.;B
Vest4		0.32
MutPred		0.15		.;.;Loss of sheet (P = 0.0104);
MVP		0.50
MPC		0.27
ClinPred		0.67	D
GERP RS		5.3
Varity_R		0.16
gMVP		0.27
Mutation Taster		=80/20	polymorphism

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: rs922050997; hg19: chr1-119427369;