10-130136449-T-G

Variant names:

• chr10-130136449-T-G
• NM_006541.5:c.29T>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006541.5(GLRX3):​c.29T>G​(p.Val10Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000631 in 1,109,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000063 (0 hom.)
• Consequence: GLRX3 NM_006541.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.211

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]

LOC105378561 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08754641).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLRX3	NM_006541.5	c.29T>G	p.Val10Gly	missense_variant	Exon 1 of 11	ENST00000331244.10	NP_006532.2
GLRX3	NM_001199868.2	c.29T>G	p.Val10Gly	missense_variant	Exon 1 of 12		NP_001186797.1
GLRX3	NM_001321980.2	c.-499T>G		5_prime_UTR_variant	Exon 1 of 12		NP_001308909.1
LOC105378561	XR_001747659.2	n.-78A>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLRX3	ENST00000331244.10	c.29T>G	p.Val10Gly	missense_variant	Exon 1 of 11	1	NM_006541.5	ENSP00000330836.5
GLRX3	ENST00000481034.1	n.29T>G		non_coding_transcript_exon_variant	Exon 1 of 13	1		ENSP00000435445.1
GLRX3	ENST00000368644.5	c.29T>G	p.Val10Gly	missense_variant	Exon 1 of 12	2		ENSP00000357633.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000631 AC: 7 AN: 1109770 Hom.: 0 Cov.: 34 AF XY: 0.00000759 AC XY: 4 AN XY: 527282

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: 0.00000753

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.29T>G (p.V10G) alteration is located in exon 1 (coding exon 1) of the GLRX3 gene. This alteration results from a T to G substitution at nucleotide position 29, causing the valine (V) at amino acid position 10 to be replaced by a glycine (G). 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	0.043
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	15
DANN	Benign	0.54
DEOGEN2	Benign	0.064	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.00096	N
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.088	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.14	N;N
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.37	N;N
REVEL	Benign	0.034
Sift	Benign	0.49	T;T
Sift4G	Benign	0.39	T;T
Polyphen		0.0030	B;B
Vest4		0.20
MutPred		0.65		Loss of stability (P = 0.0094);Loss of stability (P = 0.0094);
MVP		0.082
MPC		0.057
ClinPred		0.046	T
GERP RS		-0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.031
gMVP		0.32

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-131934713;