10-130160947-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001321980.2(GLRX3):​c.-11C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,534 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

GLRX3
NM_001321980.2 5_prime_UTR_premature_start_codon_gain

Scores

9
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.26
Variant links:
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GLRX3NM_006541.5 linkc.428C>T p.Ala143Val missense_variant Exon 4 of 11 ENST00000331244.10 NP_006532.2 O76003A0A140VJK1
GLRX3NM_001321980.2 linkc.-11C>T 5_prime_UTR_premature_start_codon_gain_variant Exon 5 of 12 NP_001308909.1
GLRX3NM_001199868.2 linkc.428C>T p.Ala143Val missense_variant Exon 4 of 12 NP_001186797.1 O76003A0A140VJK1
GLRX3NM_001321980.2 linkc.-11C>T 5_prime_UTR_variant Exon 5 of 12 NP_001308909.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GLRX3ENST00000331244.10 linkc.428C>T p.Ala143Val missense_variant Exon 4 of 11 1 NM_006541.5 ENSP00000330836.5 O76003
GLRX3ENST00000481034.1 linkn.428C>T non_coding_transcript_exon_variant Exon 4 of 13 1 ENSP00000435445.1 O76003
GLRX3ENST00000368644.5 linkc.428C>T p.Ala143Val missense_variant Exon 4 of 12 2 ENSP00000357633.1 O76003
GLRX3ENST00000486974.1 linkn.*74C>T downstream_gene_variant 5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461534
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727090
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.069
T
BayesDel_noAF
Benign
-0.34
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.49
T;T
Eigen
Benign
0.16
Eigen_PC
Uncertain
0.23
FATHMM_MKL
Uncertain
0.94
D
M_CAP
Benign
0.0051
T
MetaRNN
Uncertain
0.48
T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Uncertain
2.2
M;M
PrimateAI
Uncertain
0.71
T
PROVEAN
Uncertain
-2.9
D;D
REVEL
Benign
0.21
Sift
Benign
0.041
D;D
Sift4G
Uncertain
0.013
D;D
Polyphen
0.65
P;P
Vest4
0.72
MutPred
0.24
Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);
MVP
0.30
MPC
0.17
ClinPred
0.98
D
GERP RS
4.4
Varity_R
0.39
gMVP
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-131959211; API