10-130136473-C-T

Variant names:

• chr10-130136473-C-T
• rs1444560109
• NM_006541.5:c.53C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006541.5(GLRX3):​c.53C>T​(p.Ser18Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000395 in 1,266,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: GLRX3 NM_006541.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.04
• 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]

ENSG00000300559 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39220768).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006541.5. 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.53C>T	p.Ser18Leu	missense	Exon 1 of 11	NP_006532.2	A0A140VJK1
	GLRX3	NM_001199868.2		c.53C>T	p.Ser18Leu	missense	Exon 1 of 12	NP_001186797.1	O76003
	GLRX3	NM_001321980.2		c.-475C>T		5_prime_UTR	Exon 1 of 12	NP_001308909.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLRX3	ENST00000331244.10	TSL:1 MANE Select	c.53C>T	p.Ser18Leu	missense	Exon 1 of 11	ENSP00000330836.5	O76003
	GLRX3	ENST00000481034.1	TSL:1	n.53C>T		non_coding_transcript_exon	Exon 1 of 13	ENSP00000435445.1	O76003
	GLRX3	ENST00000861475.1		c.53C>T	p.Ser18Leu	missense	Exon 1 of 12	ENSP00000531534.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152196 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000359 AC: 4 AN: 1113824 Hom.: 0 Cov.: 34 AF XY: 0.00000189 AC XY: 1 AN XY: 529958

African (AFR) AF: 0.00 AC: 0 AN: 23252

American (AMR) AF: 0.00 AC: 0 AN: 9466

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14810

East Asian (EAS) AF: 0.00 AC: 0 AN: 26844

South Asian (SAS) AF: 0.00 AC: 0 AN: 24052

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2986

European-Non Finnish (NFE) AF: 0.00000322 AC: 3 AN: 931818

Other (OTH) AF: 0.0000225 AC: 1 AN: 44522

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152196 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 74364

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	Uncertain	0.48
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.59	D
Eigen	Benign	0.070
Eigen_PC	Benign	-0.075
FATHMM_MKL	Benign	0.0047	N
M_CAP	Pathogenic	0.47	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		1.0
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.14
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.90	P
Vest4		0.23
MutPred		0.49		Loss of disorder (P = 0.0112)
MVP		0.22
MPC		0.044
ClinPred		0.98	D
GERP RS		3.9
PromoterAI		-0.0022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.56
gMVP		0.63
Mutation Taster		=67/33	polymorphism

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: rs1444560109; hg19: chr10-131934737;