rs757075712
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3PP5_Moderate
The NM_003201.3(TFAM):c.533C>T(p.Pro178Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,611,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. P178P) has been classified as Likely benign.
Frequency
Consequence
NM_003201.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TFAM | NM_003201.3 | c.533C>T | p.Pro178Leu | missense_variant | 5/7 | ENST00000487519.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TFAM | ENST00000487519.6 | c.533C>T | p.Pro178Leu | missense_variant | 5/7 | 1 | NM_003201.3 | P1 | |
TFAM | ENST00000395377.2 | c.479C>T | p.Pro160Leu | missense_variant | 5/6 | 2 | |||
TFAM | ENST00000373895.7 | c.441+2037C>T | intron_variant | 2 | |||||
TFAM | ENST00000373899.3 | n.803C>T | non_coding_transcript_exon_variant | 6/8 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152012Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250444Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135526
GnomAD4 exome AF: 0.00000548 AC: 8AN: 1459986Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 4AN XY: 726354
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152012Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74226
ClinVar
Submissions by phenotype
Mitochondrial DNA depletion syndrome 15 (hepatocerebral type) Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | UCLA Clinical Genomics Center, UCLA | Oct 01, 2015 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 20, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at