15-89333596-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP3BP6_Very_StrongBS2
The NM_001430120.1(POLGARF):c.205_213dupGCAGCAGCA(p.Ala69_Ala71dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00448 in 151,706 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_001430120.1 conservative_inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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POLG | NM_002693.3 | c.150_158dupGCAGCAGCA | p.Gln51_Gln53dup | disruptive_inframe_insertion | Exon 2 of 23 | ENST00000268124.11 | NP_002684.1 | |
POLGARF | NM_001430120.1 | c.205_213dupGCAGCAGCA | p.Ala69_Ala71dup | conservative_inframe_insertion | Exon 1 of 2 | NP_001417049.1 | ||
POLG | NM_001126131.2 | c.150_158dupGCAGCAGCA | p.Gln51_Gln53dup | disruptive_inframe_insertion | Exon 2 of 23 | NP_001119603.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
POLGARF | ENST00000706918.1 | c.205_213dupGCAGCAGCA | p.Ala69_Ala71dup | conservative_inframe_insertion | Exon 1 of 2 | ENSP00000516626.1 | ||||
POLG | ENST00000268124.11 | c.150_158dupGCAGCAGCA | p.Gln51_Gln53dup | disruptive_inframe_insertion | Exon 2 of 23 | 1 | NM_002693.3 | ENSP00000268124.5 |
Frequencies
GnomAD3 genomes AF: 0.00449 AC: 681AN: 151602Hom.: 4 Cov.: 30
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00127 AC: 1831AN: 1446392Hom.: 3 Cov.: 31 AF XY: 0.00118 AC XY: 847AN XY: 719194
GnomAD4 genome AF: 0.00448 AC: 680AN: 151706Hom.: 3 Cov.: 30 AF XY: 0.00440 AC XY: 326AN XY: 74158
ClinVar
Submissions by phenotype
not specified Benign:5
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The variant is found in POLG panel(s). -
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not provided Benign:5
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POLG: BS1, BS2 -
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Progressive sclerosing poliodystrophy;C1834846:Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1;C1843851:Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis;C3150914:Mitochondrial DNA depletion syndrome 4b;C4225153:Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1;C4551995:Mitochondrial DNA depletion syndrome 1 Benign:1
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Inborn genetic diseases Benign:1
This alteration is classified as 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. -
Progressive sclerosing poliodystrophy Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at