chr9-27157936-A-G

Variant names:

• chr9-27157936-A-G
• NM_000459.5:c.158A>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000459.5(TEK):​c.158A>G​(p.Glu53Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TEK NM_000459.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.32

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.866

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEK	NM_000459.5	c.158A>G	p.Glu53Gly	missense_variant	Exon 2 of 23	ENST00000380036.10	NP_000450.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEK	ENST00000380036.10	c.158A>G	p.Glu53Gly	missense_variant	Exon 2 of 23	1	NM_000459.5	ENSP00000369375.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461884 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T;T;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Pathogenic	0.87	D;D;D
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Benign	0.69	.;N;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.9	.;N;N
REVEL	Uncertain	0.43
Sift	Benign	0.19	.;T;T
Sift4G	Uncertain	0.015	D;T;T
Polyphen		1.0	.;D;.
Vest4		0.73
MutPred		0.75		Gain of catalytic residue at E53 (P = 0.0847);Gain of catalytic residue at E53 (P = 0.0847);Gain of catalytic residue at E53 (P = 0.0847);
MVP		0.57
MPC		0.29
ClinPred		0.74	D
GERP RS		5.9
Varity_R		0.29
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-27157934;