9-27152345-C-T

Position:

• chr9-27152345-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000459.5(TEK):​c.53-5486C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,212 control chromosomes in the GnomAD database, including 5,417 homozygotes. 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: 𝑓 0.26 (5417 hom., cov: 31)
• Consequence: TEK NM_000459.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.80

Genes affected

TEK (HGNC:11724): (TEK receptor tyrosine kinase) This gene encodes a receptor that belongs to the protein tyrosine kinase Tie2 family. The encoded protein possesses a unique extracellular region that contains two immunoglobulin-like domains, three epidermal growth factor (EGF)-like domains and three fibronectin type III repeats. The ligand angiopoietin-1 binds to this receptor and mediates a signaling pathway that functions in embryonic vascular development. Mutations in this gene are associated with inherited venous malformations of the skin and mucous membranes. Alternative splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Feb 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEK	NM_000459.5	c.53-5486C>T		intron_variant		ENST00000380036.10	NP_000450.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEK	ENST00000380036.10	c.53-5486C>T		intron_variant		1	NM_000459.5	ENSP00000369375	P1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39383 AN: 151094 Hom.: 5405 Cov.: 31

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.260

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.261 AC: 39430 AN: 151212 Hom.: 5417 Cov.: 31 AF XY: 0.265 AC XY: 19537 AN XY: 73738

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.262

Alfa AF: 0.187 Hom.: 852

Bravo AF: 0.252

Asia WGS AF: 0.397 AC: 1382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.45
DANN	Benign	0.63

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: rs664513; hg19: chr9-27152343;