rs34458027

Variant names:

• chr10-130166520-G-A
• rs34458027
• NM_006541.5:c.492G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-130166520-G-A
• chr10-130166520-G-C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_006541.5(GLRX3):​c.492G>A​(p.Gln164Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0093 in 1,612,948 control chromosomes in the GnomAD database, including 132 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0081 (11 hom., cov: 32)
  • Exomes 𝑓: 0.0094 (121 hom.)
• Consequence: GLRX3 NM_006541.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.67
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 10-130166520-G-A is Benign according to our data. Variant chr10-130166520-G-A is described in ClinVar as Benign. ClinVar VariationId is 771743.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.66 with no splicing effect.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00943 (13775/1460664) while in subpopulation MID AF = 0.0188 (108/5752). AF 95% confidence interval is 0.0159. There are 121 homozygotes in GnomAdExome4. There are 6969 alleles in the male GnomAdExome4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLRX3	NM_006541.5	MANE Select	c.492G>A	p.Gln164Gln	synonymous	Exon 5 of 11	NP_006532.2	A0A140VJK1
	GLRX3	NM_001199868.2		c.492G>A	p.Gln164Gln	synonymous	Exon 5 of 12	NP_001186797.1	O76003
	GLRX3	NM_001321980.2		c.54G>A	p.Gln18Gln	synonymous	Exon 6 of 12	NP_001308909.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLRX3	ENST00000331244.10	TSL:1 MANE Select	c.492G>A	p.Gln164Gln	synonymous	Exon 5 of 11	ENSP00000330836.5	O76003
	GLRX3	ENST00000481034.1	TSL:1	n.492G>A		non_coding_transcript_exon	Exon 5 of 13	ENSP00000435445.1	O76003
	GLRX3	ENST00000861475.1		c.585G>A	p.Gln195Gln	synonymous	Exon 6 of 12	ENSP00000531534.1

Frequencies

GnomAD3 genomes AF: 0.00810 AC: 1233 AN: 152166 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00183

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00582

Gnomad ASJ AF: 0.0703

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.00405

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.0108

Gnomad OTH AF: 0.0144

GnomAD2 exomes AF: 0.00959 AC: 2405 AN: 250738 AF XY: 0.00987

Gnomad AFR exome AF: 0.00142

Gnomad AMR exome AF: 0.00492

Gnomad ASJ exome AF: 0.0653

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00338

Gnomad NFE exome AF: 0.0117

Gnomad OTH exome AF: 0.0144

GnomAD4 exome AF: 0.00943 AC: 13775 AN: 1460664 Hom.: 121 Cov.: 29 AF XY: 0.00959 AC XY: 6969 AN XY: 726670

African (AFR) AF: 0.00152 AC: 51 AN: 33462

American (AMR) AF: 0.00528 AC: 236 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.0653 AC: 1705 AN: 26118

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39668

South Asian (SAS) AF: 0.00281 AC: 242 AN: 86200

European-Finnish (FIN) AF: 0.00399 AC: 213 AN: 53330

Middle Eastern (MID) AF: 0.0188 AC: 108 AN: 5752

European-Non Finnish (NFE) AF: 0.00945 AC: 10502 AN: 1111080

Other (OTH) AF: 0.0119 AC: 716 AN: 60350

GnomAD4 genome AF: 0.00809 AC: 1232 AN: 152284 Hom.: 11 Cov.: 32 AF XY: 0.00743 AC XY: 553 AN XY: 74464

African (AFR) AF: 0.00185 AC: 77 AN: 41552

American (AMR) AF: 0.00582 AC: 89 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0703 AC: 244 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4816

European-Finnish (FIN) AF: 0.00405 AC: 43 AN: 10618

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.0108 AC: 736 AN: 68028

Other (OTH) AF: 0.0142 AC: 30 AN: 2110

Alfa AF: 0.0117 Hom.: 26

Bravo AF: 0.00824

Asia WGS AF: 0.00144 AC: 6 AN: 3478

EpiCase AF: 0.0133

EpiControl AF: 0.0129

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	11
DANN	Benign	0.71
PhyloP100		2.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs34458027; hg19: chr10-131964784; COSMIC: COSV100487903;