chr10-130175000-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_006541.5(GLRX3):c.868C>T(p.Arg290Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000523 in 1,604,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000053 ( 0 hom. )
Consequence
GLRX3
NM_006541.5 missense
NM_006541.5 missense
Scores
10
6
2
Clinical Significance
Conservation
PhyloP100: 2.68
Genes affected
GLRX3 (HGNC:15987): (glutaredoxin 3) This gene encodes a member of the glutaredoxin family. Glutaredoxins are oxidoreductase enzymes that reduce a variety of substrates using glutathione as a cofactor. The encoded protein binds to and modulates the function of protein kinase C theta. The encoded protein may also inhibit apoptosis and play a role in cellular growth, and the expression of this gene may be a marker for cancer. Pseudogenes of this gene are located on the short arm of chromosomes 6 and 9. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Dec 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.947
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLRX3 | NM_006541.5 | c.868C>T | p.Arg290Trp | missense_variant | 10/11 | ENST00000331244.10 | |
GLRX3 | NM_001199868.2 | c.868C>T | p.Arg290Trp | missense_variant | 10/12 | ||
GLRX3 | NM_001321980.2 | c.430C>T | p.Arg144Trp | missense_variant | 11/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLRX3 | ENST00000331244.10 | c.868C>T | p.Arg290Trp | missense_variant | 10/11 | 1 | NM_006541.5 | P1 | |
GLRX3 | ENST00000481034.1 | c.868C>T | p.Arg290Trp | missense_variant, NMD_transcript_variant | 10/13 | 1 | |||
GLRX3 | ENST00000368644.5 | c.868C>T | p.Arg290Trp | missense_variant | 10/12 | 2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152054Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251430Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135892
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GnomAD4 exome AF: 0.0000530 AC: 77AN: 1452598Hom.: 0 Cov.: 28 AF XY: 0.0000553 AC XY: 40AN XY: 723318
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152054Hom.: 0 Cov.: 33 AF XY: 0.0000539 AC XY: 4AN XY: 74256
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 05, 2021 | The c.868C>T (p.R290W) alteration is located in exon 10 (coding exon 10) of the GLRX3 gene. This alteration results from a C to T substitution at nucleotide position 868, causing the arginine (R) at amino acid position 290 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Uncertain
D;D
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;H
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Loss of disorder (P = 0.0183);Loss of disorder (P = 0.0183);
MVP
MPC
0.33
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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