19-7629834-A-G
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_ModeratePS1_ModeratePM2PP5_Very_Strong
The NM_001171155.2(PET100):āc.1A>Gā(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.00000846 in 1,536,278 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (ā ā ).
Frequency
Consequence
NM_001171155.2 start_lost
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PET100 | NM_001171155.2 | c.1A>G | p.Met1? | start_lost | Exon 1 of 4 | ENST00000594797.6 | NP_001164626.1 | |
STXBP2 | NM_001414484.1 | c.-197A>G | 5_prime_UTR_variant | Exon 1 of 21 | NP_001401413.1 | |||
PET100 | NR_033242.2 | n.42A>G | non_coding_transcript_exon_variant | Exon 1 of 5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PET100 | ENST00000594797.6 | c.1A>G | p.Met1? | start_lost | Exon 1 of 4 | 1 | NM_001171155.2 | ENSP00000470539.1 | ||
ENSG00000268400 | ENST00000698368.1 | n.1A>G | non_coding_transcript_exon_variant | Exon 1 of 20 | ENSP00000513686.1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151962Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000721 AC: 1AN: 138732Hom.: 0 AF XY: 0.0000134 AC XY: 1AN XY: 74402
GnomAD4 exome AF: 0.00000867 AC: 12AN: 1384316Hom.: 0 Cov.: 31 AF XY: 0.00000878 AC XY: 6AN XY: 683110
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151962Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74224
ClinVar
Submissions by phenotype
Mitochondrial complex 4 deficiency, nuclear type 12 Pathogenic:2
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not provided Pathogenic:1
For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 1686017). Disruption of the initiator codon has been observed in individuals with PET100-related conditions (PMID: 24462369, 31406627, 32313153). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change affects the initiator methionine of the PET100 mRNA. The next in-frame methionine is located at codon 10. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at