chrX-24699491-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS1_Supporting
The NM_001330360.2(POLA1):c.110G>A(p.Arg37His) variant causes a missense change. The variant allele was found at a frequency of 0.00005 in 1,180,803 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. 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. R37S) has been classified as Likely benign.
Frequency
Consequence
NM_001330360.2 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 |
---|---|---|---|---|---|---|---|
POLA1 | NM_001330360.2 | c.110G>A | p.Arg37His | missense_variant | 2/37 | ENST00000379068.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLA1 | ENST00000379068.8 | c.110G>A | p.Arg37His | missense_variant | 2/37 | 5 | NM_001330360.2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000360 AC: 4AN: 111019Hom.: 0 Cov.: 22 AF XY: 0.0000301 AC XY: 1AN XY: 33251
GnomAD3 exomes AF: 0.0000256 AC: 4AN: 156472Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 46986
GnomAD4 exome AF: 0.0000514 AC: 55AN: 1069735Hom.: 0 Cov.: 25 AF XY: 0.0000440 AC XY: 15AN XY: 340633
GnomAD4 genome ? AF: 0.0000360 AC: 4AN: 111068Hom.: 0 Cov.: 22 AF XY: 0.0000300 AC XY: 1AN XY: 33310
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 10, 2022 | The c.92G>A (p.R31H) alteration is located in exon 2 (coding exon 2) of the POLA1 gene. This alteration results from a G to A substitution at nucleotide position 92, causing the arginine (R) at amino acid position 31 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 28, 2021 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with POLA1-related conditions. This variant is present in population databases (rs371458274, ExAC 0.03%). This sequence change replaces arginine with histidine at codon 31 of the POLA1 protein (p.Arg31His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at