Variant 10-130160914-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006541.5(GLRX3):c.395A>T(p.Asp132Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000477 in 1,613,578 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

GLRX3
NM_006541.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.74

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GLRX3	NM_006541.5 linkuse as main transcript	c.395A>T	p.Asp132Val	missense_variant	4/11	ENST00000331244.10
GLRX3	NM_001199868.2 linkuse as main transcript	c.395A>T	p.Asp132Val	missense_variant	4/12
GLRX3	NM_001321980.2 linkuse as main transcript	c.-44A>T		5_prime_UTR_variant	5/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GLRX3	ENST00000331244.10 linkuse as main transcript	c.395A>T	p.Asp132Val	missense_variant	4/11	1	NM_006541.5	P1
GLRX3	ENST00000481034.1 linkuse as main transcript	c.395A>T	p.Asp132Val	missense_variant, NMD_transcript_variant	4/13	1
GLRX3	ENST00000368644.5 linkuse as main transcript	c.395A>T	p.Asp132Val	missense_variant	4/12	2		P1
GLRX3	ENST00000486974.1 linkuse as main transcript			downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251428

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000458

AC:

AN:

1461382

Hom.:

Cov.:

AF XY:

0.0000440

AC XY:

AN XY:

727040

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000576

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

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

May 17, 2023

The c.395A>T (p.D132V) alteration is located in exon 4 (coding exon 4) of the GLRX3 gene. This alteration results from a A to T substitution at nucleotide position 395, causing the aspartic acid (D) at amino acid position 132 to be replaced by a valine (V). 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

0.25

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.21

Cadd

Uncertain

Dann

Uncertain

0.98

DEOGEN2

Uncertain

0.46

T;T

Eigen

Benign

-0.097

Eigen_PC

Benign

0.034

FATHMM_MKL

Uncertain

0.93

M_CAP

Benign

0.0071

MetaRNN

Uncertain

0.52

D;D

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.2

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.3

D;D

REVEL

Benign

0.24

Sift

Benign

0.093

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.29

B;B

Vest4

0.72

MVP

0.49

MPC

0.086

ClinPred

0.45

GERP RS

4.4

Varity_R

0.36

gMVP

0.73

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