10-130160947-C-T

Variant names:

• chr10-130160947-C-T
• NM_006541.5:c.428C>T

Variant summary

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

The NM_001321980.2(GLRX3):​c.-11C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,534 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: GLRX3 NM_001321980.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.26

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLRX3	NM_006541.5	c.428C>T	p.Ala143Val	missense_variant	Exon 4 of 11	ENST00000331244.10	NP_006532.2
GLRX3	NM_001321980.2	c.-11C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 5 of 12		NP_001308909.1
GLRX3	NM_001199868.2	c.428C>T	p.Ala143Val	missense_variant	Exon 4 of 12		NP_001186797.1
GLRX3	NM_001321980.2	c.-11C>T		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.428C>T	p.Ala143Val	missense_variant	Exon 4 of 11	1	NM_006541.5	ENSP00000330836.5
GLRX3	ENST00000481034.1	n.428C>T		non_coding_transcript_exon_variant	Exon 4 of 13	1		ENSP00000435445.1
GLRX3	ENST00000368644.5	c.428C>T	p.Ala143Val	missense_variant	Exon 4 of 12	2		ENSP00000357633.1
GLRX3	ENST00000486974.1	n.*74C>T		downstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461534 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727090

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T;T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.0051	T
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Benign	0.21
Sift	Benign	0.041	D;D
Sift4G	Uncertain	0.013	D;D
Polyphen		0.65	P;P
Vest4		0.72
MutPred		0.24		Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);
MVP		0.30
MPC		0.17
ClinPred		0.98	D
GERP RS		4.4
Varity_R		0.39
gMVP		0.58

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: chr10-131959211;