14-95535084-G-A
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Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_016417.3(GLRX5):c.-6G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000142 in 1,333,622 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00018 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00014 ( 0 hom. )
Consequence
GLRX5
NM_016417.3 5_prime_UTR
NM_016417.3 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.50
Genes affected
GLRX5 (HGNC:20134): (glutaredoxin 5) This gene encodes a mitochondrial protein, which is evolutionarily conserved. It is involved in the biogenesis of iron-sulfur clusters, which are required for normal iron homeostasis. Mutations in this gene are associated with autosomal recessive pyridoxine-refractory sideroblastic anemia. [provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
Variant 14-95535084-G-A is Benign according to our data. Variant chr14-95535084-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2662649.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000178 (27/152002) while in subpopulation AMR AF= 0.000851 (13/15274). AF 95% confidence interval is 0.000503. There are 1 homozygotes in gnomad4. There are 16 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLRX5 | NM_016417.3 | c.-6G>A | 5_prime_UTR_variant | 1/2 | ENST00000331334.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLRX5 | ENST00000331334.5 | c.-6G>A | 5_prime_UTR_variant | 1/2 | 1 | NM_016417.3 | P1 | ||
GLRX5 | ENST00000553672.1 | n.301+1281G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.000178 AC: 27AN: 151894Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.0000587 AC: 4AN: 68134Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 39612
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GnomAD4 exome AF: 0.000137 AC: 162AN: 1181620Hom.: 0 Cov.: 31 AF XY: 0.000146 AC XY: 85AN XY: 582496
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GnomAD4 genome AF: 0.000178 AC: 27AN: 152002Hom.: 1 Cov.: 33 AF XY: 0.000215 AC XY: 16AN XY: 74316
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 23, 2023 | Nucleotide substitution has no predicted effect on splicing and is not conserved across species; Has not been previously published as pathogenic or benign to our knowledge - |
GLRX5-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 20, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
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RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at