16-30091481-T-A

Variant names:

• chr16-30091481-T-A
• rs3809624
• ENST00000553607.1:c.-288A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000553607.1(TBX6):​c.-288A>T variant causes a 5 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TBX6 ENST00000553607.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.604
• Publications: 52 publications found

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]

TBX6 Gene-Disease associations (from GenCC):

• Mayer-Rokitansky-Kuster-Hauser syndrome

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
• spondylocostal dysostosis 5

  Inheritance: Unknown, SD, AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• autosomal dominant spondylocostal dysostosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• congenital anomaly of kidney and urinary tract

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000553607.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX6	NM_004608.4	MANE Select	c.-48-240A>T		intron	N/A	NP_004599.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBX6	ENST00000553607.1	TSL:1	c.-288A>T		5_prime_UTR	Exon 1 of 5	ENSP00000461223.1	O95947-2
	TBX6	ENST00000395224.7	TSL:1 MANE Select	c.-48-240A>T		intron	N/A	ENSP00000378650.2	O95947-1
	TBX6	ENST00000931584.1		c.-288A>T		5_prime_UTR	Exon 1 of 8	ENSP00000601643.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 173492 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 89880

African (AFR) AF: 0.00 AC: 0 AN: 4886

American (AMR) AF: 0.00 AC: 0 AN: 6938

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6250

East Asian (EAS) AF: 0.00 AC: 0 AN: 12318

South Asian (SAS) AF: 0.00 AC: 0 AN: 13264

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10126

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 870

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 107862

Other (OTH) AF: 0.00 AC: 0 AN: 10978

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Benign	0.92
PhyloP100		0.60
PromoterAI		0.025	Neutral

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3809624;

hg19: chr16-30102802;