chr10-130175033-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_006541.5(GLRX3):c.901A>T(p.Thr301Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,609,622 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 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
GLRX3
NM_006541.5 missense
NM_006541.5 missense
Scores
5
7
6
Clinical Significance
Conservation
PhyloP100: 8.23
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 Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.88
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLRX3 | NM_006541.5 | c.901A>T | p.Thr301Ser | missense_variant | 10/11 | ENST00000331244.10 | |
GLRX3 | NM_001199868.2 | c.901A>T | p.Thr301Ser | missense_variant | 10/12 | ||
GLRX3 | NM_001321980.2 | c.463A>T | p.Thr155Ser | missense_variant | 11/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLRX3 | ENST00000331244.10 | c.901A>T | p.Thr301Ser | missense_variant | 10/11 | 1 | NM_006541.5 | P1 | |
GLRX3 | ENST00000481034.1 | c.901A>T | p.Thr301Ser | missense_variant, NMD_transcript_variant | 10/13 | 1 | |||
GLRX3 | ENST00000368644.5 | c.901A>T | p.Thr301Ser | missense_variant | 10/12 | 2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152166Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251456Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135896
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GnomAD4 exome AF: 0.00000206 AC: 3AN: 1457456Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1AN XY: 725494
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152166Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74350
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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, 2023 | The c.901A>T (p.T301S) alteration is located in exon 10 (coding exon 10) of the GLRX3 gene. This alteration results from a A to T substitution at nucleotide position 901, causing the threonine (T) at amino acid position 301 to be replaced by a serine (S). 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
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
D;D
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
H;H
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
D;D
Vest4
MVP
MPC
0.28
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