10-130136483-G-T

Variant names:

• chr10-130136483-G-T
• rs13991
• NM_006541.5:c.63G>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.63G>T​(p.Gln21His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000898 in 1,114,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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: not found (cov: 34)
  • Exomes 𝑓: 9.0e-7 (0 hom.)
• Consequence: GLRX3 NM_006541.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.640
• 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=0.38410372).

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.63G>T	p.Gln21His	missense	Exon 1 of 11	NP_006532.2	A0A140VJK1
	GLRX3	NM_001199868.2		c.63G>T	p.Gln21His	missense	Exon 1 of 12	NP_001186797.1	O76003
	GLRX3	NM_001321980.2		c.-465G>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.63G>T	p.Gln21His	missense	Exon 1 of 11	ENSP00000330836.5	O76003
	GLRX3	ENST00000481034.1	TSL:1	n.63G>T		non_coding_transcript_exon	Exon 1 of 13	ENSP00000435445.1	O76003
	GLRX3	ENST00000861475.1		c.63G>T	p.Gln21His	missense	Exon 1 of 12	ENSP00000531534.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 8.98e-7 AC: 1 AN: 1114200 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 530060

African (AFR) AF: 0.00 AC: 0 AN: 23232

American (AMR) AF: 0.00 AC: 0 AN: 9512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14844

East Asian (EAS) AF: 0.00 AC: 0 AN: 26818

South Asian (SAS) AF: 0.00 AC: 0 AN: 24258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36104

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

European-Non Finnish (NFE) AF: 0.00000107 AC: 1 AN: 931922

Other (OTH) AF: 0.00 AC: 0 AN: 44524

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.034
Eigen_PC	Benign	-0.049
FATHMM_MKL	Benign	0.023	N
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.64
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.081
Sift	Benign	0.20	T
Sift4G	Benign	0.16	T
Polyphen		0.69	P
Vest4		0.039
MutPred		0.14		Gain of glycosylation at S18 (P = 0.1284)
MVP		0.24
MPC		0.046
ClinPred		0.74	D
GERP RS		2.9
PromoterAI		0.13	Neutral
Varity_R		0.36
gMVP		0.58
Mutation Taster		=96/4	polymorphism

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;