10-130166520-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_006541.5(GLRX3):c.492G>A(p.Gln164=) 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, single submitter B:1
• Conservation: PhyloP100: 2.67

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 Benign. Variant got -13 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 id is 771743.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.66 with no splicing effect.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome 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 gnomad4_exome. There are 6969 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLRX3	NM_006541.5	c.492G>A	p.Gln164=	synonymous_variant	5/11	ENST00000331244.10
GLRX3	NM_001199868.2	c.492G>A	p.Gln164=	synonymous_variant	5/12
GLRX3	NM_001321980.2	c.54G>A	p.Gln18=	synonymous_variant	6/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLRX3	ENST00000331244.10	c.492G>A	p.Gln164=	synonymous_variant	5/11	1	NM_006541.5	P1
GLRX3	ENST00000481034.1	c.492G>A	p.Gln164=	synonymous_variant, NMD_transcript_variant	5/13	1
GLRX3	ENST00000368644.5	c.492G>A	p.Gln164=	synonymous_variant	5/12	2		P1

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

GnomAD3 exomes AF: 0.00959 AC: 2405 AN: 250738 Hom.: 31 AF XY: 0.00987 AC XY: 1338 AN XY: 135534

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 SAS exome AF: 0.00216

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

Gnomad4 AFR exome AF: 0.00152

Gnomad4 AMR exome AF: 0.00528

Gnomad4 ASJ exome AF: 0.0653

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00281

Gnomad4 FIN exome AF: 0.00399

Gnomad4 NFE exome AF: 0.00945

Gnomad4 OTH exome AF: 0.0119

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

Gnomad4 AFR AF: 0.00185

Gnomad4 AMR AF: 0.00582

Gnomad4 ASJ AF: 0.0703

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.00405

Gnomad4 NFE AF: 0.0108

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.0136 Hom.: 17

Bravo AF: 0.00824

Asia WGS AF: 0.00144 AC: 6 AN: 3478

EpiCase AF: 0.0133

EpiControl AF: 0.0129

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
Cadd	Benign	11
Dann	Benign	0.71

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

LitVar

Other links and lift over

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