10-130180094-A-G

Variant names:

• chr10-130180094-A-G
• rs3750834
• ENST00000481034.1:n.*29-19A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001199868.2(GLRX3):​c.*29-19A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 131,364 control chromosomes in the GnomAD database, including 12,920 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.44 (12913 hom., cov: 30)
  • Exomes 𝑓: 0.26 (7 hom.)
• Consequence: GLRX3 NM_001199868.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79

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]

LOC124902561 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLRX3	NM_001199868.2	c.*29-19A>G		intron_variant	Intron 11 of 11		NP_001186797.1
LOC124902561	XM_047426136.1	c.-6428A>G		upstream_gene_variant			XP_047282092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLRX3	ENST00000481034.1	n.*29-19A>G		intron_variant	Intron 11 of 12	1		ENSP00000435445.1
GLRX3	ENST00000368644.5	c.*29-19A>G		intron_variant	Intron 11 of 11	2		ENSP00000357633.1
GLRX3	ENST00000496195.1	n.48-19A>G		intron_variant	Intron 1 of 1	2
GLRX3	ENST00000619341.1	n.-91A>G		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.443 AC: 58097 AN: 131204 Hom.: 12891 Cov.: 30

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.448

GnomAD4 exome AF: 0.263 AC: 21 AN: 80 Hom.: 7 Cov.: 0 AF XY: 0.250 AC XY: 16 AN XY: 64

Gnomad4 EAS exome AF: 0.125

Gnomad4 NFE exome AF: 0.294

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.443 AC: 58160 AN: 131284 Hom.: 12913 Cov.: 30 AF XY: 0.445 AC XY: 28166 AN XY: 63244

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.352

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.448

Alfa AF: 0.295 Hom.: 9884

Bravo AF: 0.412

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.012
DANN	Benign	0.61

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3750834; hg19: chr10-131978358;