rs1862562415

Variant names:

• chr10-130160872-G-A
• rs1862562415
• NM_006541.5:c.353G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001321980.2(GLRX3):​c.-86G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GLRX3 NM_001321980.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.43
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321980.2. 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.353G>A	p.Ser118Asn	missense	Exon 4 of 11	NP_006532.2	A0A140VJK1
	GLRX3	NM_001321980.2		c.-86G>A		5_prime_UTR_premature_start_codon_gain	Exon 5 of 12	NP_001308909.1
	GLRX3	NM_001199868.2		c.353G>A	p.Ser118Asn	missense	Exon 4 of 12	NP_001186797.1	O76003

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLRX3	ENST00000331244.10	TSL:1 MANE Select	c.353G>A	p.Ser118Asn	missense	Exon 4 of 11	ENSP00000330836.5	O76003
	GLRX3	ENST00000481034.1	TSL:1	n.353G>A		non_coding_transcript_exon	Exon 4 of 13	ENSP00000435445.1	O76003
	GLRX3	ENST00000861475.1		c.446G>A	p.Ser149Asn	missense	Exon 5 of 12	ENSP00000531534.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.064	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.65	D
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	L
PhyloP100		3.4
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.10
Sift	Benign	0.070	T
Sift4G	Benign	0.33	T
Polyphen		0.0	B
Vest4		0.20
MutPred		0.24		Loss of glycosylation at S118 (P = 0.0635)
MVP		0.15
MPC		0.045
ClinPred		0.18	T
GERP RS		2.4
Varity_R		0.12
gMVP		0.37
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.24		Position offset: 19

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

Other links and lift over

dbSNP: rs1862562415; hg19: chr10-131959136;