Genetic Variant GLRX3:p.Gln21His (chr10-130136483-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_006541.5(GLRX3):c.63G>T(p.Gln21His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000898 in 1,114,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 9.0e-7 ( 0 hom. )

Consequence

GLRX3
NM_006541.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.640

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38410372).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLRX3	NM_006541.5 link	c.63G>T	p.Gln21His	missense_variant	Exon 1 of 11	ENST00000331244.10	NP_006532.2	O76003A0A140VJK1
GLRX3	NM_001199868.2 link	c.63G>T	p.Gln21His	missense_variant	Exon 1 of 12		NP_001186797.1	O76003A0A140VJK1
GLRX3	NM_001321980.2 link	c.-465G>T		5_prime_UTR_variant	Exon 1 of 12		NP_001308909.1
LOC105378561	XR_001747659.2 link	n.-112C>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GLRX3	ENST00000331244.10 link	c.63G>T	p.Gln21His	missense_variant	Exon 1 of 11	1	NM_006541.5	ENSP00000330836.5	O76003
GLRX3	ENST00000481034.1 link	n.63G>T		non_coding_transcript_exon_variant	Exon 1 of 13	1		ENSP00000435445.1	O76003
GLRX3	ENST00000368644.5 link	c.63G>T	p.Gln21His	missense_variant	Exon 1 of 12	2		ENSP00000357633.1	O76003
ENSG00000300559	ENST00000772722.1 link	n.-153C>A		upstream_gene_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.98e-7

AC:

AN:

1114200

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

530060

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23232

American (AMR)

AF:

0.00

AC:

AN:

9512

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14844

East Asian (EAS)

AF:

0.00

AC:

AN:

26818

South Asian (SAS)

AF:

0.00

AC:

AN:

24258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36104

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2986

European-Non Finnish (NFE)

AF:

0.00000107

AC:

AN:

931922

Other (OTH)

AF:

0.00

AC:

AN:

44524

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

T;T

Eigen

Benign

-0.034

Eigen_PC

Benign

-0.049

FATHMM_MKL

Benign

0.023

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.38

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L

PhyloP100

0.64

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.82

N;N

REVEL

Benign

0.081

Sift

Benign

0.20

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.69

P;P

Vest4

0.039

MutPred

0.14

Gain of glycosylation at S18 (P = 0.1284);Gain of glycosylation at S18 (P = 0.1284);

MVP

0.24

MPC

0.046

ClinPred

0.74

GERP RS

2.9

PromoterAI

0.13

Neutral

(source)

Varity_R

0.36

gMVP

0.58

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over