Variant 10-130166543-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006541.5(GLRX3):c.515A>G(p.His172Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GLRX3
NM_006541.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.01

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]

GLRX3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18992838).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GLRX3	NM_006541.5 linkuse as main transcript	c.515A>G	p.His172Arg	missense_variant	5/11	ENST00000331244.10
GLRX3	NM_001199868.2 linkuse as main transcript	c.515A>G	p.His172Arg	missense_variant	5/12
GLRX3	NM_001321980.2 linkuse as main transcript	c.77A>G	p.His26Arg	missense_variant	6/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GLRX3	ENST00000331244.10 linkuse as main transcript	c.515A>G	p.His172Arg	missense_variant	5/11	1	NM_006541.5	P1
GLRX3	ENST00000481034.1 linkuse as main transcript	c.515A>G	p.His172Arg	missense_variant, NMD_transcript_variant	5/13	1
GLRX3	ENST00000368644.5 linkuse as main transcript	c.515A>G	p.His172Arg	missense_variant	5/12	2		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461202

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726924

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 18, 2023

The c.515A>G (p.H172R) alteration is located in exon 5 (coding exon 5) of the GLRX3 gene. This alteration results from a A to G substitution at nucleotide position 515, causing the histidine (H) at amino acid position 172 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Uncertain

0.030

BayesDel_noAF

Benign

-0.19

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.22

T;T

Eigen

Benign

-0.031

Eigen_PC

Benign

0.13

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.0048

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.22

Sift

Benign

0.35

T;T

Sift4G

Benign

0.37

T;T

Polyphen

0.0030

B;B

Vest4

0.34

MutPred

0.41

Gain of methylation at K171 (P = 0.0579);Gain of methylation at K171 (P = 0.0579);

MVP

0.27

MPC

0.069

ClinPred

0.89

GERP RS

5.0

Varity_R

0.55

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over