chr10-130136483-G-C

Variant names:

• chr10-130136483-G-C
• rs13991
• NM_006541.5:c.63G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006541.5(GLRX3):​c.63G>C​(p.Gln21His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,266,212 control chromosomes in the GnomAD database, including 24,691 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.18 (2526 hom., cov: 34)
  • Exomes 𝑓: 0.20 (22165 hom.)
• Consequence: GLRX3 NM_006541.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.640
• Publications: 16 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016697645).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLRX3	NM_006541.5	c.63G>C	p.Gln21His	missense_variant	Exon 1 of 11	ENST00000331244.10	NP_006532.2
GLRX3	NM_001199868.2	c.63G>C	p.Gln21His	missense_variant	Exon 1 of 12		NP_001186797.1
GLRX3	NM_001321980.2	c.-465G>C		5_prime_UTR_variant	Exon 1 of 12		NP_001308909.1
LOC105378561	XR_001747659.2	n.-112C>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLRX3	ENST00000331244.10	c.63G>C	p.Gln21His	missense_variant	Exon 1 of 11	1	NM_006541.5	ENSP00000330836.5
GLRX3	ENST00000481034.1	n.63G>C		non_coding_transcript_exon_variant	Exon 1 of 13	1		ENSP00000435445.1
GLRX3	ENST00000368644.5	c.63G>C	p.Gln21His	missense_variant	Exon 1 of 12	2		ENSP00000357633.1
ENSG00000300559	ENST00000772722.1	n.-153C>G		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26739 AN: 152130 Hom.: 2524 Cov.: 34

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.171

GnomAD2 exomes AF: 0.160 AC: 3208 AN: 20032 AF XY: 0.165

Gnomad AFR exome AF: 0.0990

Gnomad AMR exome AF: 0.0415

Gnomad ASJ exome AF: 0.170

Gnomad EAS exome AF: 0.0866

Gnomad FIN exome AF: 0.186

Gnomad NFE exome AF: 0.160

Gnomad OTH exome AF: 0.116

GnomAD4 exome AF: 0.196 AC: 218844 AN: 1113970 Hom.: 22165 Cov.: 34 AF XY: 0.197 AC XY: 104161 AN XY: 529934

African (AFR) AF: 0.128 AC: 2963 AN: 23230

American (AMR) AF: 0.111 AC: 1060 AN: 9510

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 3525 AN: 14840

East Asian (EAS) AF: 0.0893 AC: 2396 AN: 26818

South Asian (SAS) AF: 0.218 AC: 5274 AN: 24224

European-Finnish (FIN) AF: 0.194 AC: 6988 AN: 36014

Middle Eastern (MID) AF: 0.245 AC: 732 AN: 2986

European-Non Finnish (NFE) AF: 0.201 AC: 187022 AN: 931832

Other (OTH) AF: 0.200 AC: 8884 AN: 44516

GnomAD4 genome AF: 0.176 AC: 26749 AN: 152242 Hom.: 2526 Cov.: 34 AF XY: 0.177 AC XY: 13164 AN XY: 74438

African (AFR) AF: 0.134 AC: 5582 AN: 41544

American (AMR) AF: 0.134 AC: 2053 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 884 AN: 3468

East Asian (EAS) AF: 0.114 AC: 586 AN: 5160

South Asian (SAS) AF: 0.242 AC: 1169 AN: 4830

European-Finnish (FIN) AF: 0.213 AC: 2263 AN: 10620

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13704 AN: 67998

Other (OTH) AF: 0.174 AC: 368 AN: 2116

Alfa AF: 0.0969 Hom.: 117

Bravo AF: 0.166

TwinsUK AF: 0.204 AC: 757

ALSPAC AF: 0.206 AC: 795

ESP6500AA AF: 0.0987 AC: 308

ESP6500EA AF: 0.160 AC: 885

ExAC AF: 0.107 AC: 2216

Asia WGS AF: 0.204 AC: 709 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	-0.034
Eigen_PC	Benign	-0.049
FATHMM_MKL	Benign	0.024	N
MetaRNN	Benign	0.0017	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.8	L;L
PhyloP100		0.64
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.82	N;N
REVEL	Benign	0.081
Sift	Benign	0.20	T;T
Sift4G	Benign	0.16	T;T
Polyphen		0.69	P;P
Vest4		0.039
MutPred		0.14		Gain of glycosylation at S18 (P = 0.1284);Gain of glycosylation at S18 (P = 0.1284);
MPC		0.046
ClinPred		0.087	T
GERP RS		2.9
PromoterAI		-0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.36
gMVP		0.58
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs13991; hg19: chr10-131934747; COSMIC: COSV58693999; COSMIC: COSV58693999;