16-30086225-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_004608.4(TBX6):c.1311A>T(p.Ter437CysextTer81) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TBX6 NM_004608.4 stop_lost
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:1
• Conservation: PhyloP100: 2.65

Genes affected

TBX6 (HGNC:11605): (T-box transcription factor 6) This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. Knockout studies in mice indicate that this gene is important for specification of paraxial mesoderm structures. [provided by RefSeq, Aug 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 16-30086225-T-A is Pathogenic according to our data. Variant chr16-30086225-T-A is described in ClinVar as [Pathogenic]. Clinvar id is 100633.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.0621168).. Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBX6	NM_004608.4	c.1311A>T	p.Ter437CysextTer81	stop_lost	9/9	ENST00000395224.7
TBX6	XM_011545926.4	c.1311A>T	p.Ter437CysextTer81	stop_lost	9/9
TBX6	XM_047434551.1	c.1311A>T	p.Ter437CysextTer81	stop_lost	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBX6	ENST00000395224.7	c.1311A>T	p.Ter437CysextTer81	stop_lost	9/9	1	NM_004608.4	P1
TBX6	ENST00000279386.6	c.1311A>T	p.Ter437CysextTer81	stop_lost	8/8	1		P1
TBX6	ENST00000567664.5	c.*445A>T		3_prime_UTR_variant, NMD_transcript_variant	7/7	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Spondylocostal dysostosis 5 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 15, 2013

- -

Spondylocostal dysostosis 2, autosomal recessive Other:1

not provided, no classification provided

literature only

GeneReviews

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
Cadd	Benign	16
Dann	Benign	0.72
Eigen	Pathogenic	0.78
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.84	D
MutationTaster	Benign	1.0	N;N
Vest4		0.25
GERP RS		4.7

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: rs587777113; hg19: chr16-30097546;