6-30915004-G-T
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_020442.6(VARS2):c.168G>T(p.Ala56=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 1,613,132 control chromosomes in the GnomAD database, including 93,559 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.28 ( 6844 hom., cov: 32)
Exomes 𝑓: 0.34 ( 86715 hom. )
Consequence
VARS2
NM_020442.6 synonymous
NM_020442.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.205
Genes affected
VARS2 (HGNC:21642): (valyl-tRNA synthetase 2, mitochondrial) This gene encodes a mitochondrial aminoacyl-tRNA synthetase, which catalyzes the attachment of valine to tRNA(Val) for mitochondrial translation. Mutations in this gene cause combined oxidative phosphorylation deficiency-20, and are also associated with early-onset mitochondrial encephalopathies. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
?
Variant 6-30915004-G-T is Benign according to our data. Variant chr6-30915004-G-T is described in ClinVar as [Benign]. Clinvar id is 380150.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.205 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VARS2 | NM_020442.6 | c.168G>T | p.Ala56= | synonymous_variant | 2/30 | ENST00000676266.1 | |
VARS2 | NM_001167734.2 | c.258G>T | p.Ala86= | synonymous_variant | 2/30 | ||
VARS2 | NM_001167733.3 | c.-219-152G>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VARS2 | ENST00000676266.1 | c.168G>T | p.Ala56= | synonymous_variant | 2/30 | NM_020442.6 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.280 AC: 42566AN: 151960Hom.: 6847 Cov.: 32
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GnomAD3 exomes AF: 0.317 AC: 78291AN: 247178Hom.: 13257 AF XY: 0.324 AC XY: 43563AN XY: 134538
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GnomAD4 exome AF: 0.339 AC: 495848AN: 1461056Hom.: 86715 Cov.: 53 AF XY: 0.339 AC XY: 246547AN XY: 726846
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GnomAD4 genome ? AF: 0.280 AC: 42576AN: 152076Hom.: 6844 Cov.: 32 AF XY: 0.281 AC XY: 20879AN XY: 74310
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Feb 19, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 16, 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. - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at