chrX-24699490-C-A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001330360.2(POLA1):c.109C>A(p.Arg37Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000849 in 1,177,537 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 20 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R37H) has been classified as Uncertain significance.
Frequency
Consequence
NM_001330360.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLA1 | NM_001330360.2 | c.109C>A | p.Arg37Ser | missense_variant | 2/37 | ENST00000379068.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLA1 | ENST00000379068.8 | c.109C>A | p.Arg37Ser | missense_variant | 2/37 | 5 | NM_001330360.2 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000335 AC: 37AN: 110592Hom.: 0 Cov.: 22 AF XY: 0.000213 AC XY: 7AN XY: 32906
GnomAD3 exomes AF: 0.000141 AC: 22AN: 156056Hom.: 0 AF XY: 0.0000643 AC XY: 3AN XY: 46654
GnomAD4 exome AF: 0.0000591 AC: 63AN: 1066889Hom.: 0 Cov.: 25 AF XY: 0.0000384 AC XY: 13AN XY: 338393
GnomAD4 genome AF: 0.000334 AC: 37AN: 110648Hom.: 0 Cov.: 22 AF XY: 0.000212 AC XY: 7AN XY: 32972
ClinVar
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 08, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 08, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at