rs10757641

Positions:

• chr9-27212362-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.2687-345C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 152,160 control chromosomes in the GnomAD database, including 51,391 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 0.82 (51391 hom., cov: 32)
• Consequence: TEK NM_000459.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEK	NM_000459.5	c.2687-345C>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.2687-345C>T		intron_variant		1	NM_000459.5	ENSP00000369375	P1
TEK	ENST00000406359.8	c.2558-345C>T		intron_variant		2		ENSP00000383977
TEK	ENST00000519097.5	c.2243-345C>T		intron_variant		2		ENSP00000430686
TEK	ENST00000615002.4	c.*1188-345C>T		intron_variant		5		ENSP00000480251

Frequencies

GnomAD3 genomes AF: 0.819 AC: 124582 AN: 152042 Hom.: 51333 Cov.: 32

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.859

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 0.884

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.827

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

GnomAD4 genome AF: 0.820 AC: 124700 AN: 152160 Hom.: 51391 Cov.: 32 AF XY: 0.821 AC XY: 61046 AN XY: 74394

Gnomad4 AFR AF: 0.897

Gnomad4 AMR AF: 0.860

Gnomad4 ASJ AF: 0.863

Gnomad4 EAS AF: 0.883

Gnomad4 SAS AF: 0.822

Gnomad4 FIN AF: 0.735

Gnomad4 NFE AF: 0.771

Gnomad4 OTH AF: 0.828

Alfa AF: 0.793 Hom.: 46910

Bravo AF: 0.831

Asia WGS AF: 0.851 AC: 2953 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.17
DANN	Benign	0.64

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: rs10757641; hg19: chr9-27212360;