12-95494076-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_006838.4(METAP2):c.449C>T(p.Thr150Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000138 in 1,613,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_006838.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
METAP2 | NM_006838.4 | c.449C>T | p.Thr150Ile | missense_variant | 5/11 | ENST00000323666.10 | NP_006829.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
METAP2 | ENST00000323666.10 | c.449C>T | p.Thr150Ile | missense_variant | 5/11 | 1 | NM_006838.4 | ENSP00000325312.5 |
Frequencies
GnomAD3 genomes AF: 0.000191 AC: 29AN: 152068Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000147 AC: 37AN: 251218Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135768
GnomAD4 exome AF: 0.000132 AC: 193AN: 1461634Hom.: 0 Cov.: 30 AF XY: 0.000121 AC XY: 88AN XY: 727122
GnomAD4 genome AF: 0.000191 AC: 29AN: 152068Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13AN XY: 74280
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 13, 2022 | The c.449C>T (p.T150I) alteration is located in exon 5 (coding exon 5) of the METAP2 gene. This alteration results from a C to T substitution at nucleotide position 449, causing the threonine (T) at amino acid position 150 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at