10-130179361-A-C

Position:

• chr10-130179361-A-C

Variant summary

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

The NM_006541.5(GLRX3):​c.977A>C​(p.Glu326Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GLRX3 NM_006541.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.17

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]

ACMG classification

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	UniProt
GLRX3	NM_006541.5	c.977A>C	p.Glu326Ala	missense_variant	11/11	ENST00000331244.10
GLRX3	NM_001199868.2	c.977A>C	p.Glu326Ala	missense_variant	11/12
GLRX3	NM_001321980.2	c.539A>C	p.Glu180Ala	missense_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLRX3	ENST00000331244.10	c.977A>C	p.Glu326Ala	missense_variant	11/11	1	NM_006541.5	P1
GLRX3	ENST00000481034.1	c.977A>C	p.Glu326Ala	missense_variant, NMD_transcript_variant	11/13	1
GLRX3	ENST00000368644.5	c.977A>C	p.Glu326Ala	missense_variant	11/12	2		P1
GLRX3	ENST00000496195.1			upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 20

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 13, 2022

The c.977A>C (p.E326A) alteration is located in exon 11 (coding exon 11) of the GLRX3 gene. This alteration results from a A to C substitution at nucleotide position 977, causing the glutamic acid (E) at amino acid position 326 to be replaced by an alanine (A). 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	Uncertain	0.36
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.56	D;D
Eigen	Pathogenic	0.72
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Pathogenic	4.0	H;H
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-4.9	D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.010	D;D
Polyphen		0.97	D;D
Vest4		0.59
MutPred		0.61		Loss of disorder (P = 0.0433);Loss of disorder (P = 0.0433);
MVP		0.45
MPC		0.27
ClinPred		1.0	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.66
gMVP		0.82

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-131977625;