chr10-129766915-T-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_002412.5(MGMT):c.542T>C(p.Leu181Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L181F) has been classified as Uncertain significance.
Frequency
Consequence
NM_002412.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MGMT | NM_002412.5 | c.542T>C | p.Leu181Ser | missense_variant | 5/5 | ENST00000651593.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MGMT | ENST00000651593.1 | c.542T>C | p.Leu181Ser | missense_variant | 5/5 | NM_002412.5 | P1 | ||
MGMT | ENST00000306010.8 | c.635T>C | p.Leu212Ser | missense_variant | 5/5 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 249770Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135444
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461102Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726846
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74362
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 23, 2023 | The c.635T>C (p.L212S) alteration is located in exon 5 (coding exon 5) of the MGMT gene. This alteration results from a T to C substitution at nucleotide position 635, causing the leucine (L) at amino acid position 212 to be replaced by a serine (S). 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