chr9-27212764-G-A
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM2PM5PP3_StrongPP5_Moderate
The NM_000459.5(TEK):c.2744G>A(p.Arg915His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R915C) has been classified as Likely benign.
Frequency
Consequence
NM_000459.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TEK | NM_000459.5 | c.2744G>A | p.Arg915His | missense_variant | Exon 17 of 23 | ENST00000380036.10 | NP_000450.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TEK | ENST00000380036.10 | c.2744G>A | p.Arg915His | missense_variant | Exon 17 of 23 | 1 | NM_000459.5 | ENSP00000369375.4 | ||
TEK | ENST00000406359.8 | c.2615G>A | p.Arg872His | missense_variant | Exon 16 of 22 | 2 | ENSP00000383977.4 | |||
TEK | ENST00000519097.5 | c.2300G>A | p.Arg767His | missense_variant | Exon 15 of 21 | 2 | ENSP00000430686.1 | |||
TEK | ENST00000615002.4 | c.*1245G>A | 3_prime_UTR_variant | Exon 17 of 23 | 5 | ENSP00000480251.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461856Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727238
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Multiple cutaneous and mucosal venous malformations Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 01, 2010 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital | Oct 07, 2021 | This variant has been previously reported in individuals with sporadically occurring venous malformations (PMID: 19888299 and others). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at