rs1281855483

Variant names:

• chr10-130136425-C-A
• rs1281855483
• NM_006541.5:c.5C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-130136425-C-A
• chr10-130136425-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_006541.5(GLRX3):​c.5C>A​(p.Ala2Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000908 in 1,101,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 9.1e-7 (0 hom.)
• Consequence: GLRX3 NM_006541.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.697
• Publications: 0 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]

ENSG00000300559 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM1: In a modified_residue N-acetylalanine (size 0) in uniprot entity GLRX3_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31813312).

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.5C>A	p.Ala2Glu	missense	Exon 1 of 11	NP_006532.2	A0A140VJK1
	GLRX3	NM_001199868.2		c.5C>A	p.Ala2Glu	missense	Exon 1 of 12	NP_001186797.1	O76003
	GLRX3	NM_001321980.2		c.-523C>A		5_prime_UTR	Exon 1 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.5C>A	p.Ala2Glu	missense	Exon 1 of 11	ENSP00000330836.5	O76003
	GLRX3	ENST00000481034.1	TSL:1	n.5C>A		non_coding_transcript_exon	Exon 1 of 13	ENSP00000435445.1	O76003
	GLRX3	ENST00000861475.1		c.5C>A	p.Ala2Glu	missense	Exon 1 of 12	ENSP00000531534.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 9.08e-7 AC: 1 AN: 1101806 Hom.: 0 Cov.: 34 AF XY: 0.00000192 AC XY: 1 AN XY: 522082

African (AFR) AF: 0.00 AC: 0 AN: 23104

American (AMR) AF: 0.00 AC: 0 AN: 8906

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14526

East Asian (EAS) AF: 0.00 AC: 0 AN: 26678

South Asian (SAS) AF: 0.00 AC: 0 AN: 21386

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34928

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2946

European-Non Finnish (NFE) AF: 0.00000108 AC: 1 AN: 925236

Other (OTH) AF: 0.00 AC: 0 AN: 44096

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.060	T
Eigen	Benign	0.019
Eigen_PC	Benign	0.061
FATHMM_MKL	Benign	0.047	N
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.70
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.12
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.023	D
Polyphen		0.82	P
Vest4		0.37
MutPred		0.25		Loss of helix (P = 0.0376)
MVP		0.21
MPC		0.096
ClinPred		0.87	D
GERP RS		3.9
PromoterAI		-0.72	Under-expression
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.31
gMVP		0.42
Mutation Taster		=68/32	polymorphism

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

Other links and lift over

dbSNP: rs1281855483; hg19: chr10-131934689;