rs146301349
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7
The NM_002693.3(POLG):c.3652C>T(p.Leu1218=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000731 in 1,613,442 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. L1218L) has been classified as Likely benign.
Frequency
Consequence
NM_002693.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLG | NM_002693.3 | c.3652C>T | p.Leu1218= | synonymous_variant | 23/23 | ENST00000268124.11 | |
FANCI | NM_001113378.2 | c.*360G>A | 3_prime_UTR_variant | 38/38 | ENST00000310775.12 | ||
POLGARF | NM_001406557.1 | c.*2924C>T | 3_prime_UTR_variant | 23/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLG | ENST00000268124.11 | c.3652C>T | p.Leu1218= | synonymous_variant | 23/23 | 1 | NM_002693.3 | P1 | |
FANCI | ENST00000310775.12 | c.*360G>A | 3_prime_UTR_variant | 38/38 | 1 | NM_001113378.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000283 AC: 43AN: 152156Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000716 AC: 18AN: 251352Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135856
GnomAD4 exome AF: 0.0000513 AC: 75AN: 1461168Hom.: 0 Cov.: 30 AF XY: 0.0000523 AC XY: 38AN XY: 726980
GnomAD4 genome ? AF: 0.000282 AC: 43AN: 152274Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20AN XY: 74462
ClinVar
Submissions by phenotype
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.3652C>T (NP_002684.1:p.Leu1218=) [GRCH38: NC_000015.10:g.89316819G>A] variant in FANCI 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 FANCI 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 11, 2024 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 22, 2018 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 21, 2014 | 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 | Jan 24, 2023 | 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). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at