Genetic Variant GLRX3:p.Ala2Val (chr10-130136425-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM1BP4_Moderate

The NM_006541.5(GLRX3):c.5C>T(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000012 in 1,254,040 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 0.000072 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

GLRX3
NM_006541.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.697

Publications

0 publications found

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:

ENSG00000300559 (HGNC:):

ENSG00000300559 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM1

In a modified_residue N-acetylalanine (size 0) in uniprot entity GLRX3_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.23190734).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006541.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GLRX3	NM_006541.5	MANE Select	c.5C>T	p.Ala2Val	missense	Exon 1 of 11	NP_006532.2	A0A140VJK1
GLRX3	NM_001199868.2		c.5C>T	p.Ala2Val	missense	Exon 1 of 12	NP_001186797.1	O76003
GLRX3	NM_001321980.2		c.-523C>T		5_prime_UTR	Exon 1 of 12	NP_001308909.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GLRX3	ENST00000331244.10	TSL:1 MANE Select	c.5C>T	p.Ala2Val	missense	Exon 1 of 11	ENSP00000330836.5	O76003
GLRX3	ENST00000481034.1	TSL:1	n.5C>T		non_coding_transcript_exon	Exon 1 of 13	ENSP00000435445.1	O76003
GLRX3	ENST00000861475.1		c.5C>T	p.Ala2Val	missense	Exon 1 of 12	ENSP00000531534.1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000363

AC:

AN:

1101806

Hom.:

Cov.:

AF XY:

0.00000383

AC XY:

AN XY:

522082

show subpopulations

African (AFR)

AF:

0.0000433

AC:

AN:

23104

American (AMR)

AF:

0.000112

AC:

AN:

8906

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14526

East Asian (EAS)

AF:

0.00

AC:

AN:

26678

South Asian (SAS)

AF:

0.00

AC:

AN:

21386

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34928

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2946

European-Non Finnish (NFE)

AF:

0.00000108

AC:

AN:

925236

Other (OTH)

AF:

0.0000227

AC:

AN:

44096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0000723

AC:

AN:

41472

American (AMR)

AF:

0.000458

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000945

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.056

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.049

FATHMM_MKL

Benign

0.019

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.34

PhyloP100

0.70

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.22

REVEL

Benign

0.10

Sift

Uncertain

0.021

Sift4G

Uncertain

0.030

Polyphen

0.67

Vest4

0.30

MutPred

0.27

Loss of helix (P = 0.079)

MVP

0.22

MPC

0.055

ClinPred

0.89

GERP RS

3.9

PromoterAI

-0.57

Under-expression

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.21

gMVP

0.42

Mutation Taster

=69/31

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over