Genetic Variant NM_197962.3:c.451C>T (chr1-193096669-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_197962.3(GLRX2):c.451C>T(p.His151Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000612 in 1,596,092 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 0.00051 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00062 ( 0 hom. )

Consequence

GLRX2
NM_197962.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.72

Publications

2 publications found

Variant links:

Genes affected

GLRX2 (HGNC:16065): (glutaredoxin 2) The protein encoded by this gene is a member of the glutaredoxin family of proteins, which maintain cellular thiol homeostasis. These proteins are thiol-disulfide oxidoreductases that use a glutathione-binding site and one or two active cysteines in their active site. This gene undergoes alternative splicing to produce multiple isoforms, one of which is ubiquitously expressed and localizes to mitochondria, where it functions in mitochondrial redox homeostasis and is important for the protection against and recovery from oxidative stress. Other isoforms, which have more restrictive expression patterns, show cytosolic and nuclear localization, and are thought to function in cellular differentiation and transformation, possibly with a role in tumor progression. [provided by RefSeq, Aug 2011]

GLRX2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09922877).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_197962.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GLRX2	NM_197962.3	MANE Select	c.451C>T	p.His151Tyr	missense	Exon 4 of 4	NP_932066.1	Q9NS18-1
GLRX2	NM_016066.4		c.454C>T	p.His152Tyr	missense	Exon 4 of 4	NP_057150.2	Q9NS18-2
GLRX2	NM_001243399.2		c.331C>T	p.His111Tyr	missense	Exon 4 of 4	NP_001230328.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GLRX2	ENST00000367439.8	TSL:1 MANE Select	c.451C>T	p.His151Tyr	missense	Exon 4 of 4	ENSP00000356409.3	Q9NS18-1
GLRX2	ENST00000367440.3	TSL:1	c.454C>T	p.His152Tyr	missense	Exon 4 of 4	ENSP00000356410.3	Q9NS18-2
GLRX2	ENST00000472197.1	TSL:5	n.772C>T		splice_region non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes

AF:

0.000513

AC:

AN:

152010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.000378

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000941

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000460

AC:

115

AN:

250042

AF XY:

0.000451

show subpopulations

Gnomad AFR exome

AF:

0.0000621

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.000849

Gnomad OTH exome

AF:

0.000821

GnomAD4 exome

AF:

0.000623

AC:

900

AN:

1443964

Hom.:

Cov.:

AF XY:

0.000606

AC XY:

436

AN XY:

719396

show subpopulations

African (AFR)

AF:

0.0000906

AC:

AN:

33120

American (AMR)

AF:

0.000157

AC:

AN:

44526

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25956

East Asian (EAS)

AF:

0.00

AC:

AN:

39526

South Asian (SAS)

AF:

0.000117

AC:

AN:

85704

European-Finnish (FIN)

AF:

0.000356

AC:

AN:

53340

Middle Eastern (MID)

AF:

0.000524

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.000743

AC:

814

AN:

1096284

Other (OTH)

AF:

0.000736

AC:

AN:

59788

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

113

150

188

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

112

140

<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:

0.000506

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41506

American (AMR)

AF:

0.000196

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000208

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.000378

AC:

AN:

10572

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000927

AC:

AN:

67992

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000782

Hom.:

Bravo

AF:

0.000431

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000461

AC:

EpiCase

AF:

0.00126

EpiControl

AF:

0.000356

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.041

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.76

M_CAP

Benign

0.011

MetaRNN

Benign

0.099

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.6

PhyloP100

4.7

PrimateAI

Benign

0.37

PROVEAN

Benign

-2.0

REVEL

Benign

0.098

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.0060

Polyphen

0.70

Vest4

0.28

MVP

0.52

MPC

0.60

ClinPred

0.16

GERP RS

5.5

Varity_R

0.62

gMVP

0.51

Mutation Taster

=76/24

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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