10-130136461-A-T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_006541.5(GLRX3):c.41A>T(p.Glu14Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000018 in 1,112,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GLRX3
NM_006541.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.300

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:

LOC105378561 (HGNC:):

LOC105378561 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09887567).

BP6

Variant 10-130136461-A-T is Benign according to our data. Variant chr10-130136461-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 3520667.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLRX3	NM_006541.5 link	c.41A>T	p.Glu14Val	missense_variant	Exon 1 of 11	ENST00000331244.10	NP_006532.2	O76003A0A140VJK1
GLRX3	NM_001199868.2 link	c.41A>T	p.Glu14Val	missense_variant	Exon 1 of 12		NP_001186797.1	O76003A0A140VJK1
GLRX3	NM_001321980.2 link	c.-487A>T		5_prime_UTR_variant	Exon 1 of 12		NP_001308909.1
LOC105378561	XR_001747659.2 link	n.-90T>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GLRX3	ENST00000331244.10 link	c.41A>T	p.Glu14Val	missense_variant	Exon 1 of 11	1	NM_006541.5	ENSP00000330836.5	O76003
GLRX3	ENST00000481034.1 link	n.41A>T		non_coding_transcript_exon_variant	Exon 1 of 13	1		ENSP00000435445.1	O76003
GLRX3	ENST00000368644.5 link	c.41A>T	p.Glu14Val	missense_variant	Exon 1 of 12	2		ENSP00000357633.1	O76003

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152100

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000180

AC:

AN:

1112238

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

528912

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:

0.0000850

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000657

AC:

AN:

152100

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Oct 08, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.032

T;T

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.00031

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.099

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.1

L;L

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

1.5

N;N

REVEL

Benign

0.039

Sift

Benign

0.31

T;T

Sift4G

Benign

0.30

T;T

Polyphen

0.0

B;B

Vest4

0.096

MutPred

0.47

Loss of disorder (P = 0.0057);Loss of disorder (P = 0.0057);

MVP

0.093

MPC

0.052

ClinPred

0.12

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.27

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