17-37097957-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM5PP2BP4_ModerateBS2
The NM_198834.3(ACACA):c.6593G>A(p.Arg2198Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000128 in 1,614,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. R2198W) has been classified as Pathogenic.
Frequency
Consequence
NM_198834.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACACA | NM_198834.3 | c.6593G>A | p.Arg2198Gln | missense_variant | 53/56 | ENST00000616317.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACACA | ENST00000616317.5 | c.6593G>A | p.Arg2198Gln | missense_variant | 53/56 | 1 | NM_198834.3 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000191 AC: 48AN: 251470Hom.: 0 AF XY: 0.000177 AC XY: 24AN XY: 135910
GnomAD4 exome AF: 0.000130 AC: 190AN: 1461888Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 98AN XY: 727246
GnomAD4 genome AF: 0.000105 AC: 16AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74358
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 2161 of the ACACA protein (p.Arg2161Gln). This variant is present in population databases (rs149967550, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with ACACA-related conditions. ClinVar contains an entry for this variant (Variation ID: 1900468). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at