rs1060504037
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong
The NM_001406557.1(POLGARF):c.85C>T(p.Arg29Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,535,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 6/9 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R29Q) has been classified as Likely benign.
Frequency
Consequence
NM_001406557.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLGARF | NM_001406557.1 | c.85C>T | p.Arg29Trp | missense_variant | 2/23 | ||
POLG | NM_002693.3 | c.30C>T | p.Ala10= | synonymous_variant | 2/23 | ENST00000268124.11 | |
POLG | NM_001126131.2 | c.30C>T | p.Ala10= | synonymous_variant | 2/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLGARF | ENST00000706918.1 | c.85C>T | p.Arg29Trp | missense_variant | 1/2 | P1 | |||
POLG | ENST00000268124.11 | c.30C>T | p.Ala10= | synonymous_variant | 2/23 | 1 | NM_002693.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152136Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000459 AC: 6AN: 130826Hom.: 0 AF XY: 0.0000419 AC XY: 3AN XY: 71596
GnomAD4 exome AF: 0.0000130 AC: 18AN: 1383738Hom.: 0 Cov.: 32 AF XY: 0.0000146 AC XY: 10AN XY: 682984
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152136Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74308
ClinVar
Submissions by phenotype
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
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 01, 2021 | - - |
Progressive sclerosing poliodystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at