Variant 5-95816609-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The ENST00000237858.11(GLRX):c.225T>C(p.Ile75=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 1,580,096 control chromosomes in the GnomAD database, including 125,296 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.37 ( 10776 hom., cov: 31)

Exomes 𝑓: 0.40 ( 114520 hom. )

Consequence

GLRX
ENST00000237858.11 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.15

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 Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP7

Synonymous conserved (PhyloP=-1.14 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GLRX	NM_001118890.2 linkuse as main transcript	c.225T>C	p.Ile75=	synonymous_variant	2/3	ENST00000237858.11	NP_001112362.1
GLRX	NM_001243658.2 linkuse as main transcript	c.225T>C	p.Ile75=	synonymous_variant	2/3		NP_001230587.1
GLRX	NM_001243659.2 linkuse as main transcript	c.225T>C	p.Ile75=	synonymous_variant	2/3		NP_001230588.1
GLRX	NM_002064.3 linkuse as main transcript	c.225T>C	p.Ile75=	synonymous_variant	2/3		NP_002055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLRX	ENST00000237858.11 linkuse as main transcript	c.225T>C	p.Ile75=	synonymous_variant	2/3	1	NM_001118890.2	ENSP00000237858	P1

Frequencies

GnomAD3 genomes

AF:

0.371

AC:

56350

AN:

151844

Hom.:

10779

Cov.:

show subpopulations

Gnomad AFR

AF:

0.329

Gnomad AMI

AF:

0.422

Gnomad AMR

AF:

0.310

Gnomad ASJ

AF:

0.419

Gnomad EAS

AF:

0.178

Gnomad SAS

AF:

0.367

Gnomad FIN

AF:

0.374

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.393

GnomAD3 exomes

AF:

0.363

AC:

91306

AN:

251296

Hom.:

17568

AF XY:

0.373

AC XY:

50684

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.324

Gnomad AMR exome

AF:

0.222

Gnomad ASJ exome

AF:

0.415

Gnomad EAS exome

AF:

0.181

Gnomad SAS exome

AF:

0.387

Gnomad FIN exome

AF:

0.384

Gnomad NFE exome

AF:

0.425

Gnomad OTH exome

AF:

0.388

GnomAD4 exome

AF:

0.395

AC:

564812

AN:

1428134

Hom.:

114520

Cov.:

AF XY:

0.397

AC XY:

282892

AN XY:

712506

show subpopulations

Gnomad4 AFR exome

AF:

0.313

Gnomad4 AMR exome

AF:

0.232

Gnomad4 ASJ exome

AF:

0.412

Gnomad4 EAS exome

AF:

0.162

Gnomad4 SAS exome

AF:

0.387

Gnomad4 FIN exome

AF:

0.386

Gnomad4 NFE exome

AF:

0.414

Gnomad4 OTH exome

AF:

0.387

GnomAD4 genome

AF:

0.371

AC:

56369

AN:

151962

Hom.:

10776

Cov.:

AF XY:

0.367

AC XY:

27291

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.329

Gnomad4 AMR

AF:

0.310

Gnomad4 ASJ

AF:

0.419

Gnomad4 EAS

AF:

0.179

Gnomad4 SAS

AF:

0.368

Gnomad4 FIN

AF:

0.374

Gnomad4 NFE

AF:

0.421

Gnomad4 OTH

AF:

0.392

Alfa

AF:

0.410

Hom.:

21241

Bravo

AF:

0.363

Asia WGS

AF:

0.264

AC:

919

AN:

3478

EpiCase

AF:

0.433

EpiControl

AF:

0.431

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.096

DANN

Benign

0.49

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over