10-130136425-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_006541.5(GLRX3):c.5C>T(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000012 in 1,254,040 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: 𝑓 0.000072 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

GLRX3
NM_006541.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.697

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 2 ACMG points.

PM1

In a modified_residue N-acetylalanine (size 0) in uniprot entity GLRX3_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23190734).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GLRX3	NM_006541.5 linkuse as main transcript	c.5C>T	p.Ala2Val	missense_variant	1/11	ENST00000331244.10
GLRX3	NM_001199868.2 linkuse as main transcript	c.5C>T	p.Ala2Val	missense_variant	1/12
GLRX3	NM_001321980.2 linkuse as main transcript	c.-523C>T		5_prime_UTR_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GLRX3	ENST00000331244.10 linkuse as main transcript	c.5C>T	p.Ala2Val	missense_variant	1/11	1	NM_006541.5	P1
GLRX3	ENST00000481034.1 linkuse as main transcript	c.5C>T	p.Ala2Val	missense_variant, NMD_transcript_variant	1/13	1
GLRX3	ENST00000368644.5 linkuse as main transcript	c.5C>T	p.Ala2Val	missense_variant	1/12	2		P1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000363

AC:

AN:

1101806

Hom.:

Cov.:

AF XY:

0.00000383

AC XY:

AN XY:

522082

show subpopulations

Gnomad4 AFR exome

AF:

0.0000433

Gnomad4 AMR exome

AF:

0.000112

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:

0.00000108

Gnomad4 OTH exome

AF:

0.0000227

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000945

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

Jan 12, 2024

The c.5C>T (p.A2V) alteration is located in exon 1 (coding exon 1) of the GLRX3 gene. This alteration results from a C to T substitution at nucleotide position 5, causing the alanine (A) at amino acid position 2 to be replaced by a valine (V). 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

Uncertain

0.47

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.056

T;T

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.049

FATHMM_MKL

Benign

0.019

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.34

N;N

MutationTaster

Benign

0.97

D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.22

N;N

REVEL

Benign

0.10

Sift

Uncertain

0.021

D;D

Sift4G

Uncertain

0.030

D;D

Polyphen

0.67

P;P

Vest4

0.30

MutPred

0.27

Loss of helix (P = 0.079);Loss of helix (P = 0.079);

MVP

0.22

MPC

0.055

ClinPred

0.89

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.21

gMVP

0.42

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over