15-89333596-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBA1
The NM_001430120.1(POLGARF):c.208_213dupGCAGCA(p.Ala70_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 0.0296 in 1,598,052 control chromosomes in the GnomAD database, including 545 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 -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
POLG | NM_002693.3 | c.153_158dupGCAGCA | p.Gln52_Gln53dup | disruptive_inframe_insertion | Exon 2 of 23 | ENST00000268124.11 | NP_002684.1 | |
POLGARF | NM_001430120.1 | c.208_213dupGCAGCA | p.Ala70_Ala71dup | conservative_inframe_insertion | Exon 1 of 2 | NP_001417049.1 | ||
POLG | NM_001126131.2 | c.153_158dupGCAGCA | p.Gln52_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.208_213dupGCAGCA | p.Ala70_Ala71dup | conservative_inframe_insertion | Exon 1 of 2 | ENSP00000516626.1 | ||||
POLG | ENST00000268124.11 | c.153_158dupGCAGCA | p.Gln52_Gln53dup | disruptive_inframe_insertion | Exon 2 of 23 | 1 | NM_002693.3 | ENSP00000268124.5 |
Frequencies
GnomAD3 genomes AF: 0.0394 AC: 5975AN: 151578Hom.: 173 Cov.: 30
GnomAD4 exome AF: 0.0286 AC: 41298AN: 1446370Hom.: 372 Cov.: 31 AF XY: 0.0278 AC XY: 19979AN XY: 719178
GnomAD4 genome AF: 0.0394 AC: 5974AN: 151682Hom.: 173 Cov.: 30 AF XY: 0.0381 AC XY: 2826AN XY: 74144
ClinVar
Submissions by phenotype
not provided Benign:4
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Autosomal recessive progressive external ophthalmoplegia Benign:1
African/African American population allele frequency is 7.411% (rs41550117, 3143/41176 alleles, 127 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.5.1, this variant is classified as BENIGN. Following criteria are met: BA1 -
not specified Benign:1
The variant is found in CHILD-EPI panel(s). -
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. -
Hereditary spastic paraplegia Benign:1
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Progressive sclerosing poliodystrophy Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at