1-193096669-G-A

Position:

chr1-193096669-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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

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 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=0.09922877).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLRX2	NM_197962.3 link	c.451C>T	p.His151Tyr	missense_variant	4/4	ENST00000367439.8	NP_932066.1	Q9NS18-1
GLRX2	NM_016066.4 link	c.454C>T	p.His152Tyr	missense_variant	4/4		NP_057150.2	Q9NS18-2
GLRX2	NM_001243399.2 link	c.331C>T	p.His111Tyr	missense_variant	4/4		NP_001230328.1	Q9NS18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GLRX2	ENST00000367439.8 link	c.451C>T	p.His151Tyr	missense_variant	4/4	1	NM_197962.3	ENSP00000356409.3	Q9NS18-1
GLRX2	ENST00000367440.3 link	c.454C>T	p.His152Tyr	missense_variant	4/4	1		ENSP00000356410.3	Q9NS18-2
GLRX2	ENST00000472197.1 link	n.772C>T		splice_region_variant, non_coding_transcript_exon_variant	4/4	5
GLRX2	ENST00000608166.2 link	n.451C>T		non_coding_transcript_exon_variant	4/5	6		ENSP00000494652.1	Q9NS18-1

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

GnomAD3 exomes

AF:

0.000460

AC:

115

AN:

250042

Hom.:

AF XY:

0.000451

AC XY:

AN XY:

135202

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 SAS exome

AF:

0.0000987

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

Gnomad4 AFR exome

AF:

0.0000906

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000117

Gnomad4 FIN exome

AF:

0.000356

Gnomad4 NFE exome

AF:

0.000743

Gnomad4 OTH exome

AF:

0.000736

GnomAD4 genome

AF:

0.000506

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.000378

Gnomad4 NFE

AF:

0.000927

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000805

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

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

Oct 06, 2022

The c.454C>T (p.H152Y) alteration is located in exon 4 (coding exon 4) of the GLRX2 gene. This alteration results from a C to T substitution at nucleotide position 454, causing the histidine (H) at amino acid position 152 to be replaced by a tyrosine (Y). 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

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.041

T;.

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.099

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.6

L;.

PrimateAI

Benign

0.37

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.098

Sift

Uncertain

0.0080

D;D

Sift4G

Uncertain

0.0060

D;D

Polyphen

0.70

P;D

Vest4

0.28

MVP

0.52

MPC

0.60

ClinPred

0.16

GERP RS

5.5

Varity_R

0.62

gMVP

0.51

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