1-43272988-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_144626.3(TMEM125):c.266C>T(p.Ser89Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000744 in 1,612,308 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S89W) has been classified as Uncertain significance.
Frequency
Consequence
NM_144626.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TMEM125 | ENST00000439858.6 | c.266C>T | p.Ser89Leu | missense_variant | Exon 4 of 4 | 2 | NM_144626.3 | ENSP00000429775.1 | ||
TMEM125 | ENST00000432792.6 | c.266C>T | p.Ser89Leu | missense_variant | Exon 4 of 4 | 1 | ENSP00000429275.1 | |||
TMEM125 | ENST00000456751.1 | c.*219C>T | downstream_gene_variant | 3 | ENSP00000428627.1 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152186Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000401 AC: 10AN: 249452Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135058
GnomAD4 exome AF: 0.0000760 AC: 111AN: 1460122Hom.: 0 Cov.: 31 AF XY: 0.0000868 AC XY: 63AN XY: 726150
GnomAD4 genome AF: 0.0000591 AC: 9AN: 152186Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74348
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.266C>T (p.S89L) alteration is located in exon 4 (coding exon 1) of the TMEM125 gene. This alteration results from a C to T substitution at nucleotide position 266, causing the serine (S) at amino acid position 89 to be replaced by a leucine (L). 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