rs543910258
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6_Very_StrongBP7
The NM_002693.3(POLG):c.1965G>A(p.Leu655=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,613,136 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. L655L) 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 -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLG | NM_002693.3 | c.1965G>A | p.Leu655= | synonymous_variant | 11/23 | ENST00000268124.11 | |
POLGARF | NM_001406557.1 | c.*1237G>A | 3_prime_UTR_variant | 11/23 | |||
POLG | NM_001126131.2 | c.1965G>A | p.Leu655= | synonymous_variant | 11/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLG | ENST00000268124.11 | c.1965G>A | p.Leu655= | synonymous_variant | 11/23 | 1 | NM_002693.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152254Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000482 AC: 12AN: 249076Hom.: 0 AF XY: 0.0000297 AC XY: 4AN XY: 134794
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1460764Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8AN XY: 726702
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152372Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2AN XY: 74512
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 23, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
POLG-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 09, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Progressive sclerosing poliodystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at