10-130160926-G-C

Variant names:

• chr10-130160926-G-C
• NM_006541.5:c.407G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006541.5(GLRX3):​c.407G>C​(p.Arg136Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. R136H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GLRX3 NM_006541.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.17

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.842

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLRX3	NM_006541.5	c.407G>C	p.Arg136Pro	missense_variant	Exon 4 of 11	ENST00000331244.10	NP_006532.2
GLRX3	NM_001199868.2	c.407G>C	p.Arg136Pro	missense_variant	Exon 4 of 12		NP_001186797.1
GLRX3	NM_001321980.2	c.-32G>C		5_prime_UTR_variant	Exon 5 of 12		NP_001308909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLRX3	ENST00000331244.10	c.407G>C	p.Arg136Pro	missense_variant	Exon 4 of 11	1	NM_006541.5	ENSP00000330836.5
GLRX3	ENST00000481034.1	n.407G>C		non_coding_transcript_exon_variant	Exon 4 of 13	1		ENSP00000435445.1
GLRX3	ENST00000368644.5	c.407G>C	p.Arg136Pro	missense_variant	Exon 4 of 12	2		ENSP00000357633.1
GLRX3	ENST00000486974.1	n.*53G>C		downstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.77	D;D
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.0043	T
MetaRNN	Pathogenic	0.84	D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-5.5	D;D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;D
Vest4		0.91
MutPred		0.51		Gain of ubiquitination at K139 (P = 0.0408);Gain of ubiquitination at K139 (P = 0.0408);
MVP		0.53
MPC		0.37
ClinPred		1.0	D
GERP RS		4.4
Varity_R		0.95
gMVP		0.93

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-131959190;