chr1-54758048-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_152268.4(PARS2):c.1114G>A(p.Ala372Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000768 in 1,613,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A372A) has been classified as Likely benign.
Frequency
Consequence
NM_152268.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PARS2 | NM_152268.4 | c.1114G>A | p.Ala372Thr | missense_variant | 2/2 | ENST00000371279.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PARS2 | ENST00000371279.4 | c.1114G>A | p.Ala372Thr | missense_variant | 2/2 | 1 | NM_152268.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152114Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000917 AC: 23AN: 250874Hom.: 0 AF XY: 0.000111 AC XY: 15AN XY: 135630
GnomAD4 exome AF: 0.0000807 AC: 118AN: 1461706Hom.: 0 Cov.: 32 AF XY: 0.0000949 AC XY: 69AN XY: 727142
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152114Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74298
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2023 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 998644). This variant has not been reported in the literature in individuals affected with PARS2-related conditions. This variant is present in population databases (rs759058241, gnomAD 0.02%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 372 of the PARS2 protein (p.Ala372Thr). - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 07, 2020 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 13, 2023 | The c.1114G>A (p.A372T) alteration is located in exon 2 (coding exon 1) of the PARS2 gene. This alteration results from a G to A substitution at nucleotide position 1114, causing the alanine (A) at amino acid position 372 to be replaced by a threonine (T). 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