rs201789237
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_138773.4(SLC25A46):āc.887A>Gā(p.Asn296Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000744 in 1,613,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_138773.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC25A46 | NM_138773.4 | c.887A>G | p.Asn296Ser | missense_variant | 8/8 | ENST00000355943.8 | |
SLC25A46 | NM_001303250.3 | c.614A>G | p.Asn205Ser | missense_variant | 8/8 | ||
SLC25A46 | NM_001303249.3 | c.679-35A>G | intron_variant | ||||
SLC25A46 | NR_138151.2 | n.1126A>G | non_coding_transcript_exon_variant | 9/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC25A46 | ENST00000355943.8 | c.887A>G | p.Asn296Ser | missense_variant | 8/8 | 1 | NM_138773.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152102Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 250528Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135368
GnomAD4 exome AF: 0.0000807 AC: 118AN: 1461524Hom.: 0 Cov.: 32 AF XY: 0.0000853 AC XY: 62AN XY: 727066
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74424
ClinVar
Submissions by phenotype
Neuropathy, hereditary motor and sensory, type 6B Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 15, 2022 | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 296 of the SLC25A46 protein (p.Asn296Ser). This variant is present in population databases (rs201789237, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with SLC25A46-related conditions. ClinVar contains an entry for this variant (Variation ID: 542448). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at