5-95816527-C-T

Position:

chr5-95816527-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001118890.2(GLRX):c.307G>A(p.Gly103Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000266 in 1,578,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

GLRX
NM_001118890.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.10

Variant links:

Genes affected

GLRX (HGNC:4330): (glutaredoxin) This gene encodes a member of the glutaredoxin family. The encoded protein is a cytoplasmic enzyme catalyzing the reversible reduction of glutathione-protein mixed disulfides. This enzyme highly contributes to the antioxidant defense system. It is crucial for several signalling pathways by controlling the S-glutathionylation status of signalling mediators. It is involved in beta-amyloid toxicity and Alzheimer's disease. Multiple alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Aug 2011]

GLRX links:

RHOBTB3 (HGNC:18757): (Rho related BTB domain containing 3) Enables ATP binding activity and small GTPase binding activity. Involved in retrograde transport, endosome to Golgi. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

RHOBTB3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.753

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLRX	NM_001118890.2 link	c.307G>A	p.Gly103Arg	missense_variant	2/3	ENST00000237858.11	NP_001112362.1	P35754A0A024RAM2
GLRX	NM_001243658.2 link	c.307G>A	p.Gly103Arg	missense_variant	2/3		NP_001230587.1	P35754A0A024RAM2
GLRX	NM_001243659.2 link	c.307G>A	p.Gly103Arg	missense_variant	2/3		NP_001230588.1	P35754A0A024RAM2
GLRX	NM_002064.3 link	c.307G>A	p.Gly103Arg	missense_variant	2/3		NP_002055.1	P35754A0A024RAM2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLRX	ENST00000237858.11 link	c.307G>A	p.Gly103Arg	missense_variant	2/3	1	NM_001118890.2	ENSP00000237858.6		P35754

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000358

AC:

AN:

251422

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000259

AC:

AN:

1425996

Hom.:

Cov.:

AF XY:

0.0000225

AC XY:

AN XY:

711640

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000351

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000297

Gnomad4 OTH exome

AF:

0.0000338

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.0000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

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 19, 2024

The c.307G>A (p.G103R) alteration is located in exon 2 (coding exon 2) of the GLRX gene. This alteration results from a G to A substitution at nucleotide position 307, causing the glycine (G) at amino acid position 103 to be replaced by an arginine (R). 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

0.34

BayesDel_addAF

Benign

-0.079

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.80

D;D;D;D;D

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.74

.;.;.;.;T

M_CAP

Benign

0.028

MetaRNN

Pathogenic

0.75

D;D;D;D;D

MetaSVM

Benign

-0.67

MutationAssessor

Pathogenic

3.0

M;M;M;M;M

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-6.2

D;D;D;D;D

REVEL

Benign

0.24

Sift

Benign

0.039

D;D;D;D;D

Sift4G

Uncertain

0.029

D;D;D;D;D

Polyphen

0.93

P;P;P;P;P

Vest4

0.68

MutPred

0.49

Gain of MoRF binding (P = 9e-04);Gain of MoRF binding (P = 9e-04);Gain of MoRF binding (P = 9e-04);Gain of MoRF binding (P = 9e-04);Gain of MoRF binding (P = 9e-04);

MVP

0.53

MPC

0.49

ClinPred

0.46

GERP RS

4.1

Varity_R

0.69

gMVP

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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