NM_006541.5:c.41A>C

Variant names:

• chr10-130136461-A-C
• NM_006541.5:c.41A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006541.5(GLRX3):​c.41A>C​(p.Glu14Ala) variant causes a missense 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. 14/21 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. E14V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: GLRX3 NM_006541.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300

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]

LOC105378561 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07548568).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLRX3	NM_006541.5	c.41A>C	p.Glu14Ala	missense_variant	Exon 1 of 11	ENST00000331244.10	NP_006532.2
GLRX3	NM_001199868.2	c.41A>C	p.Glu14Ala	missense_variant	Exon 1 of 12		NP_001186797.1
GLRX3	NM_001321980.2	c.-487A>C		5_prime_UTR_variant	Exon 1 of 12		NP_001308909.1
LOC105378561	XR_001747659.2	n.-90T>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLRX3	ENST00000331244.10	c.41A>C	p.Glu14Ala	missense_variant	Exon 1 of 11	1	NM_006541.5	ENSP00000330836.5
GLRX3	ENST00000481034.1	n.41A>C		non_coding_transcript_exon_variant	Exon 1 of 13	1		ENSP00000435445.1
GLRX3	ENST00000368644.5	c.41A>C	p.Glu14Ala	missense_variant	Exon 1 of 12	2		ENSP00000357633.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.66
DEOGEN2	Benign	0.041	T;T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.0017	N
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.075	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.75	N;N
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	0.53	N;N
REVEL	Benign	0.046
Sift	Benign	0.76	T;T
Sift4G	Benign	0.75	T;T
Polyphen		0.0	B;B
Vest4		0.059
MutPred		0.48		Loss of solvent accessibility (P = 0.0224);Loss of solvent accessibility (P = 0.0224);
MVP		0.068
MPC		0.049
ClinPred		0.042	T
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.096
gMVP		0.28

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: chr10-131934725;