9-32420895-T-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_002197.3(ACO1):c.838T>C(p.Phe280Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_002197.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACO1 | NM_002197.3 | c.838T>C | p.Phe280Leu | missense_variant | 8/21 | ENST00000309951.8 | |
ACO1 | NM_001278352.2 | c.838T>C | p.Phe280Leu | missense_variant | 9/22 | ||
ACO1 | NM_001362840.2 | c.838T>C | p.Phe280Leu | missense_variant | 9/22 | ||
ACO1 | XM_047423430.1 | c.862T>C | p.Phe288Leu | missense_variant | 8/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACO1 | ENST00000309951.8 | c.838T>C | p.Phe280Leu | missense_variant | 8/21 | 1 | NM_002197.3 | P1 | |
ACO1 | ENST00000379923.5 | c.838T>C | p.Phe280Leu | missense_variant | 9/22 | 5 | P1 | ||
ACO1 | ENST00000541043.5 | c.838T>C | p.Phe280Leu | missense_variant | 9/22 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152208Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251228Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135772
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461634Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9AN XY: 727110
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152208Hom.: 0 Cov.: 33 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 | Aug 15, 2023 | The c.838T>C (p.F280L) alteration is located in exon 8 (coding exon 7) of the ACO1 gene. This alteration results from a T to C substitution at nucleotide position 838, causing the phenylalanine (F) at amino acid position 280 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