Genetic Variant NM_006541.5:c.63G>C (chr10-130136483-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

Publications

16 publications found

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:

ENSG00000300559 (HGNC:):

ENSG00000300559 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006541.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GLRX3	NM_006541.5	MANE Select	c.63G>C	p.Gln21His	missense	Exon 1 of 11	NP_006532.2	A0A140VJK1
GLRX3	NM_001199868.2		c.63G>C	p.Gln21His	missense	Exon 1 of 12	NP_001186797.1	O76003
GLRX3	NM_001321980.2		c.-465G>C		5_prime_UTR	Exon 1 of 12	NP_001308909.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GLRX3	ENST00000331244.10	TSL:1 MANE Select	c.63G>C	p.Gln21His	missense	Exon 1 of 11	ENSP00000330836.5	O76003
GLRX3	ENST00000481034.1	TSL:1	n.63G>C		non_coding_transcript_exon	Exon 1 of 13	ENSP00000435445.1	O76003
GLRX3	ENST00000861475.1		c.63G>C	p.Gln21His	missense	Exon 1 of 12	ENSP00000531534.1

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

GnomAD2 exomes

AF:

0.160

AC:

3208

AN:

20032

AF XY:

0.165

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 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

African (AFR)

AF:

0.128

AC:

2963

AN:

23230

American (AMR)

AF:

0.111

AC:

1060

AN:

9510

Ashkenazi Jewish (ASJ)

AF:

0.238

AC:

3525

AN:

14840

East Asian (EAS)

AF:

0.0893

AC:

2396

AN:

26818

South Asian (SAS)

AF:

0.218

AC:

5274

AN:

24224

European-Finnish (FIN)

AF:

0.194

AC:

6988

AN:

36014

Middle Eastern (MID)

AF:

0.245

AC:

732

AN:

2986

European-Non Finnish (NFE)

AF:

0.201

AC:

187022

AN:

931832

Other (OTH)

AF:

0.200

AC:

8884

AN:

44516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

10866

21732

32599

43465

54331

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7480

14960

22440

29920

37400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.176

AC:

26749

AN:

152242

Hom.:

2526

Cov.:

AF XY:

0.177

AC XY:

13164

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.134

AC:

5582

AN:

41544

American (AMR)

AF:

0.134

AC:

2053

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.255

AC:

884

AN:

3468

East Asian (EAS)

AF:

0.114

AC:

586

AN:

5160

South Asian (SAS)

AF:

0.242

AC:

1169

AN:

4830

European-Finnish (FIN)

AF:

0.213

AC:

2263

AN:

10620

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.202

AC:

13704

AN:

67998

Other (OTH)

AF:

0.174

AC:

368

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1166

2331

3497

4662

5828

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

308

616

924

1232

1540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

Eigen

Benign

-0.034

Eigen_PC

Benign

-0.049

FATHMM_MKL

Benign

0.024

MetaRNN

Benign

0.0017

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.8

PhyloP100

0.64

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.82

REVEL

Benign

0.081

Sift

Benign

0.20

Sift4G

Benign

0.16

Polyphen

0.69

Vest4

0.039

MutPred

0.14

Gain of glycosylation at S18 (P = 0.1284)

MPC

0.046

ClinPred

0.087

GERP RS

2.9

PromoterAI

-0.011

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.36

gMVP

0.58

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over