6-5368753-C-T
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_006567.5(FARS2):c.183C>T(p.Asp61Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00178 in 1,614,100 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0041 ( 4 hom., cov: 32)
Exomes 𝑓: 0.0015 ( 3 hom. )
Consequence
FARS2
NM_006567.5 synonymous
NM_006567.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.640
Genes affected
FARS2 (HGNC:21062): (phenylalanyl-tRNA synthetase 2, mitochondrial) This gene encodes a protein that transfers phenylalanine to its cognate tRNA. This protein localizes to the mitochondrion and plays a role in mitochondrial protein translation. Mutations in this gene can cause combined oxidative phosphorylation deficiency 14 (Alpers encephalopathy). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
Variant 6-5368753-C-T is Benign according to our data. Variant chr6-5368753-C-T is described in ClinVar as [Benign]. Clinvar id is 260002.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.64 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00412 (627/152214) while in subpopulation AFR AF= 0.0117 (486/41536). AF 95% confidence interval is 0.0108. There are 4 homozygotes in gnomad4. There are 299 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FARS2 | NM_006567.5 | c.183C>T | p.Asp61Asp | synonymous_variant | 2/7 | ENST00000274680.9 | NP_006558.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FARS2 | ENST00000274680.9 | c.183C>T | p.Asp61Asp | synonymous_variant | 2/7 | 1 | NM_006567.5 | ENSP00000274680.4 | ||
FARS2 | ENST00000324331.10 | c.183C>T | p.Asp61Asp | synonymous_variant | 2/7 | 1 | ENSP00000316335.5 | |||
FARS2 | ENST00000648580.1 | n.183C>T | non_coding_transcript_exon_variant | 2/9 | ENSP00000497889.1 | |||||
FARS2 | ENST00000602691.1 | c.*41C>T | downstream_gene_variant | 3 | ENSP00000473394.1 |
Frequencies
GnomAD3 genomes AF: 0.00410 AC: 624AN: 152096Hom.: 4 Cov.: 32
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GnomAD3 exomes AF: 0.00156 AC: 392AN: 250956Hom.: 3 AF XY: 0.00140 AC XY: 190AN XY: 135660
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GnomAD4 exome AF: 0.00153 AC: 2243AN: 1461886Hom.: 3 Cov.: 32 AF XY: 0.00144 AC XY: 1044AN XY: 727242
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GnomAD4 genome AF: 0.00412 AC: 627AN: 152214Hom.: 4 Cov.: 32 AF XY: 0.00402 AC XY: 299AN XY: 74422
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Combined oxidative phosphorylation defect type 14 Benign:2
Benign, criteria provided, single submitter | clinical testing | Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine | Jun 13, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 01, 2015 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2023 | FARS2: BP4, BP7, BS1, BS2 - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at