10-130160947-C-T

Variant names:

• chr10-130160947-C-T
• rs760052026
• NM_006541.5:c.428C>T

Variant summary

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

The NM_001321980.2(GLRX3):​c.-11C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,534 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: GLRX3 NM_001321980.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.26
• 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.428C>T	p.Ala143Val	missense	Exon 4 of 11	NP_006532.2	A0A140VJK1
	GLRX3	NM_001321980.2		c.-11C>T		5_prime_UTR_premature_start_codon_gain	Exon 5 of 12	NP_001308909.1
	GLRX3	NM_001199868.2		c.428C>T	p.Ala143Val	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.428C>T	p.Ala143Val	missense	Exon 4 of 11	ENSP00000330836.5	O76003
	GLRX3	ENST00000481034.1	TSL:1	n.428C>T		non_coding_transcript_exon	Exon 4 of 13	ENSP00000435445.1	O76003
	GLRX3	ENST00000861475.1		c.521C>T	p.Ala174Val	missense	Exon 5 of 12	ENSP00000531534.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461534 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727090

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111804

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.0051	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.3
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.21
Sift	Benign	0.041	D
Sift4G	Uncertain	0.013	D
Polyphen		0.65	P
Vest4		0.72
MutPred		0.24		Gain of sheet (P = 0.039)
MVP		0.30
MPC		0.17
ClinPred		0.98	D
GERP RS		4.4
Varity_R		0.39
gMVP		0.58
Mutation Taster		=25/75	disease causing

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: rs760052026; hg19: chr10-131959211;