rs772461291
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_002693.3(POLG):c.1638C>T(p.Arg546=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,613,996 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 Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. R546R) has been classified as Likely benign.
Frequency
Consequence
NM_002693.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLG | NM_002693.3 | c.1638C>T | p.Arg546= | synonymous_variant | 9/23 | ENST00000268124.11 | |
POLGARF | NM_001406557.1 | c.*910C>T | 3_prime_UTR_variant | 9/23 | |||
POLG | NM_001126131.2 | c.1638C>T | p.Arg546= | synonymous_variant | 9/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLG | ENST00000268124.11 | c.1638C>T | p.Arg546= | synonymous_variant | 9/23 | 1 | NM_002693.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251364Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135872
GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461826Hom.: 0 Cov.: 33 AF XY: 0.0000289 AC XY: 21AN XY: 727222
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74326
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Aug 24, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 08, 2020 | - - |
Progressive sclerosing poliodystrophy Benign:2
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.1638C>T (NP_002684.1:p.Arg546=) [GRCH38: NC_000015.10:g.89326686G>A] 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 12, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at