Genetic Variant GLRX3:p.Gln21His (chr10-130136483-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006541.5(GLRX3):c.63G>C(p.Gln21His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,266,212 control chromosomes in the GnomAD database, including 24,691 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.18 ( 2526 hom., cov: 34)

Exomes 𝑓: 0.20 ( 22165 hom. )

Consequence

GLRX3
NM_006541.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.640

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:

LOC105378561 (HGNC:):

LOC105378561 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016697645).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLRX3	NM_006541.5 link	c.63G>C	p.Gln21His	missense_variant	Exon 1 of 11	ENST00000331244.10	NP_006532.2	O76003A0A140VJK1
GLRX3	NM_001199868.2 link	c.63G>C	p.Gln21His	missense_variant	Exon 1 of 12		NP_001186797.1	O76003A0A140VJK1
GLRX3	NM_001321980.2 link	c.-465G>C		5_prime_UTR_variant	Exon 1 of 12		NP_001308909.1
LOC105378561	XR_001747659.2 link	n.-112C>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GLRX3	ENST00000331244.10 link	c.63G>C	p.Gln21His	missense_variant	Exon 1 of 11	1	NM_006541.5	ENSP00000330836.5	O76003
GLRX3	ENST00000481034.1 link	n.63G>C		non_coding_transcript_exon_variant	Exon 1 of 13	1		ENSP00000435445.1	O76003
GLRX3	ENST00000368644.5 link	c.63G>C	p.Gln21His	missense_variant	Exon 1 of 12	2		ENSP00000357633.1	O76003

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26739

AN:

152130

Hom.:

2524

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.0888

Gnomad AMR

AF:

0.134

Gnomad ASJ

AF:

0.255

Gnomad EAS

AF:

0.114

Gnomad SAS

AF:

0.242

Gnomad FIN

AF:

0.213

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.202

Gnomad OTH

AF:

0.171

GnomAD3 exomes

AF:

0.160

AC:

3208

AN:

20032

Hom.:

289

AF XY:

0.165

AC XY:

1593

AN XY:

9660

show subpopulations

Gnomad AFR exome

AF:

0.0990

Gnomad AMR exome

AF:

0.0415

Gnomad ASJ exome

AF:

0.170

Gnomad EAS exome

AF:

0.0866

Gnomad SAS exome

AF:

0.158

Gnomad FIN exome

AF:

0.186

Gnomad NFE exome

AF:

0.160

Gnomad OTH exome

AF:

0.116

GnomAD4 exome

AF:

0.196

AC:

218844

AN:

1113970

Hom.:

22165

Cov.:

AF XY:

0.197

AC XY:

104161

AN XY:

529934

show subpopulations

Gnomad4 AFR exome

AF:

0.128

Gnomad4 AMR exome

AF:

0.111

Gnomad4 ASJ exome

AF:

0.238

Gnomad4 EAS exome

AF:

0.0893

Gnomad4 SAS exome

AF:

0.218

Gnomad4 FIN exome

AF:

0.194

Gnomad4 NFE exome

AF:

0.201

Gnomad4 OTH exome

AF:

0.200

GnomAD4 genome

AF:

0.176

AC:

26749

AN:

152242

Hom.:

2526

Cov.:

AF XY:

0.177

AC XY:

13164

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.134

Gnomad4 AMR

AF:

0.134

Gnomad4 ASJ

AF:

0.255

Gnomad4 EAS

AF:

0.114

Gnomad4 SAS

AF:

0.242

Gnomad4 FIN

AF:

0.213

Gnomad4 NFE

AF:

0.202

Gnomad4 OTH

AF:

0.174

Alfa

AF:

0.0969

Hom.:

117

Bravo

AF:

0.166

TwinsUK

AF:

0.204

AC:

757

ALSPAC

AF:

0.206

AC:

795

ESP6500AA

AF:

0.0987

AC:

308

ESP6500EA

AF:

0.160

AC:

885

ExAC

AF:

0.107

AC:

2216

Asia WGS

AF:

0.204

AC:

709

AN:

3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

T;T

Eigen

Benign

-0.034

Eigen_PC

Benign

-0.049

FATHMM_MKL

Benign

0.024

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.8

L;L

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.82

N;N

REVEL

Benign

0.081

Sift

Benign

0.20

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.69

P;P

Vest4

0.039

MutPred

0.14

Gain of glycosylation at S18 (P = 0.1284);Gain of glycosylation at S18 (P = 0.1284);

MPC

0.046

ClinPred

0.087

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.36

gMVP

0.58

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over