rs387907118
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1_ModeratePM2PP5_Very_Strong
The NM_001243279.3(ACSF3):c.1567C>T(p.Arg523*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,606,720 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 Pathogenic (★★).
Frequency
Consequence
NM_001243279.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000134 AC: 2AN: 149658Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251340Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135846
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1457062Hom.: 0 Cov.: 34 AF XY: 0.0000207 AC XY: 15AN XY: 724794
GnomAD4 genome AF: 0.0000134 AC: 2AN: 149658Hom.: 0 Cov.: 31 AF XY: 0.0000137 AC XY: 1AN XY: 72916
ClinVar
Submissions by phenotype
Combined malonic and methylmalonic acidemia Pathogenic:5
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This sequence change creates a premature translational stop signal (p.Arg523*) in the ACSF3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACSF3 are known to be pathogenic (PMID: 21841779, 26827111). This variant is present in population databases (rs387907118, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with combined malonic and methylmalonic aciduria (PMID: 21841779). ClinVar contains an entry for this variant (Variation ID: 31135). For these reasons, this variant has been classified as Pathogenic. -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at