rs745310138
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_001406557.1(POLGARF):āc.241A>Gā(p.Ile81Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000373 in 1,610,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 7/9 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I81T) has been classified as Uncertain significance.
Frequency
Consequence
NM_001406557.1 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 |
---|---|---|---|---|---|---|---|
POLGARF | NM_001406557.1 | c.241A>G | p.Ile81Val | missense_variant | 2/23 | ||
POLG | NM_002693.3 | c.186A>G | p.Leu62= | synonymous_variant | 2/23 | ENST00000268124.11 | |
POLG | NM_001126131.2 | c.186A>G | p.Leu62= | synonymous_variant | 2/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLGARF | ENST00000706918.1 | c.241A>G | p.Ile81Val | missense_variant | 1/2 | P1 | |||
POLG | ENST00000268124.11 | c.186A>G | p.Leu62= | synonymous_variant | 2/23 | 1 | NM_002693.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000145 AC: 22AN: 152186Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000731 AC: 18AN: 246270Hom.: 0 AF XY: 0.0000447 AC XY: 6AN XY: 134102
GnomAD4 exome AF: 0.0000261 AC: 38AN: 1458414Hom.: 0 Cov.: 32 AF XY: 0.0000179 AC XY: 13AN XY: 725690
GnomAD4 genome ? AF: 0.000145 AC: 22AN: 152186Hom.: 0 Cov.: 34 AF XY: 0.000175 AC XY: 13AN XY: 74362
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 18, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 02, 2016 | - - |
Progressive sclerosing poliodystrophy Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine | Oct 01, 2018 | The NM_002693.2:c.186A>G (NP_002684.1:p.Leu62=) [GRCH38: NC_000015.10:g.89333569T>C] variant in POLG gene is interpretated to be a Likely Benign based on ACMG guidelines (PMID: 25741868). This variant meets the following evidence codes reported in the ACMG-guideline. BP4:Computational evidence/predictors indicate no impact on the POLG structure, function, or protein-protein interaction. BP7:The variant is silent with non predicted splice impact. Based on the evidence criteria codes applied, the variant is suggested to be Likely Benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at