rs200566665
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_138773.4(SLC25A46):c.235G>A(p.Glu79Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00198 in 1,561,996 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E79D) has been classified as Uncertain significance.
Frequency
Consequence
NM_138773.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC25A46 | NM_138773.4 | c.235G>A | p.Glu79Lys | missense_variant | 1/8 | ENST00000355943.8 | |
SLC25A46 | NM_001303249.3 | c.235G>A | p.Glu79Lys | missense_variant | 1/8 | ||
SLC25A46 | NM_001303250.3 | c.10+1107G>A | intron_variant | ||||
SLC25A46 | NR_138151.2 | n.348G>A | non_coding_transcript_exon_variant | 1/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC25A46 | ENST00000355943.8 | c.235G>A | p.Glu79Lys | missense_variant | 1/8 | 1 | NM_138773.4 | P1 | |
SLC25A46 | ENST00000447245.6 | c.235G>A | p.Glu79Lys | missense_variant | 1/8 | 2 | |||
SLC25A46 | ENST00000513807.5 | c.-204+1107G>A | intron_variant | 2 | |||||
SLC25A46 | ENST00000508781.5 | n.112+1107G>A | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.00141 AC: 214AN: 151912Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.00136 AC: 227AN: 167026Hom.: 0 AF XY: 0.00120 AC XY: 108AN XY: 89762
GnomAD4 exome AF: 0.00204 AC: 2881AN: 1409962Hom.: 9 Cov.: 31 AF XY: 0.00204 AC XY: 1421AN XY: 697136
GnomAD4 genome AF: 0.00141 AC: 214AN: 152034Hom.: 1 Cov.: 33 AF XY: 0.00124 AC XY: 92AN XY: 74338
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Feb 03, 2022 | BP4 - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 12, 2023 | Observed with another variant in one individual with Parkinson disease; however, it is unknown whether these variants are on the same (in cis) or opposite (in trans) chromosomes (Liu et al., 2022); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: Liu_2022[Preprint]) - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | SLC25A46: BS2 - |
Neuropathy, hereditary motor and sensory, type 6B Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 15, 2019 | This alteration is classified as likely 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at